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PTENc.165-1G>ALikely pathogenic
Print report
Variant interpretation report

PTEN c.165-1G>A, p.?

NM_000314.8:c.165-1G>A NP_000305.3:p.? Canonical splice · intron 2 View identifiers
Classification
Likely pathogenic

Variant description:

The PTEN NM_000314.8:c.165-1G>A (NP_000305.3:p.?) splicing variant has previously been reported in somatic cancers (COSMIC; COSV64292036, n = 9 times). This variant is predicted to disrupt normal RNA processing, resulting in either an aberrant protein product or nonsense-mediated RNA decay. Based on available guidelines, this variant is considered to be Likely Pathogenic. This variant is considered to be Likely Pathogenic by the VCEP (Clingen PTEN Variant Curation Expert Panel, Clingen; ClinVar ID 187590).

Five-step scale from benign to pathogenic. This variant is likely pathogenic. Select a step to read what it means.

Likely pathogenic.A likely pathogenic classification under the recorded framework.

In plain language

Gene-level background from the recorded interpretation.

About PTEN

PTEN is a tumor suppressor gene that encodes a phosphatase converting the lipid messenger PIP3 back to PIP2 at the cell membrane, thereby restraining the AKT/mTOR signaling pathway that drives cell growth, proliferation, and survival. It is one of the most frequently mutated genes across many types of human cancer, and its loss promotes unchecked cell growth, survival, and genomic instability, partly through impaired DNA repair. Germline loss-of-function variants in PTEN cause Cowden syndrome, an inherited cancer predisposition disorder associated with elevated risk of breast and thyroid cancer.

NCBI Gene ↗ OncoKB ↗
LYFE Sciences is an AI system, and it can make mistakes. Criteria may be applied incorrectly, sources may be misread, and a confident-looking classification can still be wrong. Double-check every criterion and its underlying evidence before relying on any call.
01The reasoning

How it was classified

The recorded framework is ClinGen PTEN VCEP v3.2. The criteria and strengths shown below come from the saved assessment; this page does not recalculate the classification.

Recorded applied criteria

The applied criteria and their strengths are shown as assessed under the stated framework.

Pathogenic evidence criteria: 3 Benign evidence criteria: 0
Pathogenic criteria applied · 3
PVS1Strong
PVS1 · strong

Met, strong: VCEP assigns PVS1_Strong for reading-frame-preserving skipping of critical exon 3 after this canonical acceptor splice-site disruption.

PM2Supporting
PM2 · supporting

Met at Supporting: the variant is absent from gnomAD v2.1 and v4.1, satisfying the PTEN VCEP population-frequency requirement of <0.00001 (0.001%).

PP5Supporting
PP5 · supporting

Not applicable: the PTEN VCEP prohibits use of PP5, regardless of the available pathogenic ClinVar assertions.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Likely pathogenic

Likely Pathogenic: PVS1 (strong), PM2 (supporting), and PP5 (supporting) satisfy the PTEN VCEP framework's Rule12.

02The sources

Evidence at a glance

Evidence summaries and captured source records, where available. Missing entries should not be interpreted as negative findings.

SpliceAI score
0.976 maximum delta

Recorded SpliceAI maximum delta score: 0.976. Refer to the recorded PP3/BP4 rationale for interpretation.

No listed criterion applied SpliceAI ↗
ClinVar submissions
6 reported laboratory submissions

5 Pathogenic · 1 pathogenic. ClinVar API review status: reviewed by expert panel.

Applied · PP5 → ClinVar ↗
No screenshot for this evidence
Functional evidence
Not recorded

No standalone functional evidence summary is recorded in evidence_summary.functional.

No listed criterion applied OncoKB ↗
Somatic evidence
9 recorded samples

This variant has previously been reported in somatic cancers (COSMIC; COSV64292036, n = 9 times).

Context only COSMIC ↗
For specialists

Technical detail

ACMG/AMP criteria under ClinGen PTEN VCEP v3.2, with the data and sources behind each one.

28 criteria with recorded statuses: 3 met · 2 not met · 13 not assessed · 10 not applicable. Open any row for the full reasoning, the rule and the evidence behind it.

Pathogenic
PVS1PS1PS2PS3PS4PM1PM2PM3PM4PM5PM6PP1PP2PP3PP4PP5
Benign
BA1BS1BS2BS3BS4BP1BP2BP3BP4BP5BP6BP7
Met Not met Not assessed Not applicable

For the requested consequence/LoF criteria only, the canonical acceptor splice-site variant meets PTEN VCEP PVS1 at strong strength because the decision tree assigns PVS1_Strong to reading-frame-preserving alteration of critical exon 3.

PM4 is outside its VCEP-defined variant scope, and BP3 is explicitly not applicable in the PTEN CSPEC.

The searched PTEN VCEP file PVS1_DecisionTree_PTEN.pdf contains no exact variant-specific entry for c.165-1G>A or p.?; the adjudication therefore uses its governing decision-tree path and the case variant facts.

Only PS4, PP4, PP5, BP5, and BP6 were adjudicated.

PS4 was not assessed because the available evidence lacks the VCEP-required case-control statistics or phenotype-specificity scores.

PP4, PP5, and BP6 are not applicable under the PTEN VCEP; BP5 lacks the required alternate-diagnosis case evidence.

PP3 and BP4 are applicable in principle to this canonical splice-site variant, but the VCEP requires SpliceAl/VarSeak concordance and VarSeak evidence is unavailable.

BP7 is not applicable because the variant is at the canonical -1 splice-acceptor position, outside the VCEP's stated +7/-21 intronic scope.

Met · 3

PVS1 StrongVCEPMet, strong: VCEP assigns PVS1_Strong for reading-frame-preserving skipping of critical exon 3 after this canonical acceptor splice-site disruption. Details ▾Hide ▴
Reasoning

NM_000314.8:c.165-1G>A is a canonical acceptor splice-site disruption in the biologically relevant PTEN transcript. The case evidence identifies affected exon 3, with exon skipping predicted to preserve the reading frame and remove 45 coding nucleotides. The PTEN VCEP decision tree specifically routes a GT-AG splice-site variant with reading-frame-preserving exon skipping to the critical-region branch when the altered region is entire exon 3, 8, or 9; exon 3 is therefore a named critical exon. The pre-assigned decision-tree outcome is PVS1_Strong, so the criterion is met at strong strength rather than full very-strong strength. SpliceAI also predicts a high splice-impact score (maximum delta 0.976), consistent with the canonical splice consequence, but the strength assignment is determined by the VCEP decision tree.

VCEP rule
GT--AG 1,2 splice sites ... Exon skipping or use of a cryptic splice site preserves reading frame ... Exon is present in biologically-relevant transcript NM_000314.8 ... Truncated/altered region is critical to protein function (entire exon 3, 8 OR 9) ... PVS1_Strong
Evidence considered
  • PTEN PVS1 decision tree, canonical GT-AG splice-site path: exon skipping preserves the reading frame, exon 3 is present in biologically relevant transcript NM_000314.8, and the altered region is critical because the decision tree names entire exon 3; outcome shown as PVS1_Strong.
  • Variant-level assessment: NM_000314.8:c.165-1G>A, canonical acceptor (-1), affected exon 3 of 9, exon c.165_209, 45 coding nucleotides removed if skipped, reading frame preserved.
  • SpliceAI result for NM_000314.8:c.165-1G>A: maximum delta score 0.976, with DS_AL 0.976 and DS_AG 0.862.
Sources
cspec ↗vcep_pvs1_decisiontree_pten ↗pvs1_variant_assessmentspliceai ↗
PM2 SupportingVCEPMet at Supporting: the variant is absent from gnomAD v2.1 and v4.1, satisfying the PTEN VCEP population-frequency requirement of <0.00001 (0.001%). Details ▾Hide ▴
Reasoning

The variant is absent from gnomAD v2.1 and v4.1, and the corresponding non-cancer datasets also report absence. This satisfies the PTEN VCEP PM2 Supporting rule requiring a population allele frequency below 0.00001 (0.001%); no subpopulation contains multiple alleles requiring the alternative <0.00002 threshold.

VCEP rule
Absent in population...Databases present at <0.00001 (0.001%) allele frequency in gnomAD or another large sequenced population. If multiple alleles are present within any subpopulation, allele frequency in that subpopulation must be <0.00002 (0.002%).
Evidence considered
  • ClinGen PTEN VCEP specification v3.2, PM2 Supporting rule: absent in population; databases present at <0.00001 (0.001%) allele frequency in gnomAD or another large sequenced population, with <0.00002 (0.002%) required within a subpopulation if multiple alleles are present.
  • gnomAD v2.1 query for 10-89685269-G-A: absent; therefore no observed allele frequency and no contrary population observation.
  • gnomAD v4.1 query for 10-87925512-G-A: absent; therefore no observed allele frequency and no contrary population observation.
  • The corresponding non-cancer queries were absent from gnomAD v2.1 non-cancer and gnomAD v3.1 non-cancer; the v2.1 non-cancer source was specified as exomes-only and the v3.1 non-cancer source as genomes-only, with no allele frequency reported in either.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
PP5 SupportingVCEPNot applicable: the PTEN VCEP prohibits use of PP5, regardless of the available pathogenic ClinVar assertions. Details ▾Hide ▴
Reasoning

Expert panel Clingen PTEN Variant Curation Expert Panel, Clingen classified as Likely pathogenic.

VCEP rule
This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
Evidence considered
  • ClinGen PTEN VCEP v3.2 marks PP5 as not applicable and prohibits its use; ClinVar reports the variant as reviewed by an expert panel, but that classification cannot establish PP5 under this VCEP.
  • ClinVar expert panel classification
Sources
cspec ↗clinvar ↗

Not met · 2 · evaluated, threshold not reached

BA1 VCEPNot met: the variant is absent from gnomAD v2.1 and v4.1, rather than having a filtering allele frequency above the 0.00056 (0.056%) BA1 threshold. Details ▾Hide ▴
Reasoning

The variant is absent from gnomAD v2.1 and gnomAD v4.1, so no filtering allele frequency exceeds the PTEN VCEP BA1 threshold of >0.00056 (0.056%).

VCEP rule
gnomAD Filtering allele frequency >0.00056 (0.056%)
Evidence considered
  • ClinGen PTEN VCEP specification v3.2, BA1 rule: gnomAD Filtering allele frequency >0.00056 (0.056%).
  • gnomAD v2.1 query for 10-89685269-G-A: absent; no allele frequency reported.
  • gnomAD v4.1 query for 10-87925512-G-A: absent; no allele frequency reported.
  • The corresponding non-cancer queries were also absent from gnomAD v2.1 non-cancer and gnomAD v3.1 non-cancer; no frequency or homozygote count was reported.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
BS1 VCEPNot met: the variant is absent from gnomAD v2.1 and v4.1, with no allele frequency in either the 0.000043–0.00056 or 0.0000043–0.000043 BS1 intervals. Details ▾Hide ▴
Reasoning

The variant is absent from gnomAD v2.1 and gnomAD v4.1, so its filtering allele frequency is not within either PTEN VCEP BS1 interval: 0.000043 to 0.00056 for BS1 or 0.0000043 to 0.000043 for BS1 Supporting.

VCEP rule
gnomAD Filtering allele frequency from 0.000043 (0.0043%) up to 0.00056 (0.056%)...Allele frequency from 0.0000043 (0.00043%) up to 0.000043 (0.0043%).
Evidence considered
  • ClinGen PTEN VCEP specification v3.2, BS1 strong rule: gnomAD Filtering allele frequency from 0.000043 (0.0043%) up to 0.00056 (0.056%).
  • ClinGen PTEN VCEP specification v3.2, BS1 Supporting rule: Allele frequency from 0.0000043 (0.00043%) up to 0.000043 (0.0043%).
  • gnomAD v2.1 query for 10-89685269-G-A: absent; no allele frequency reported.
  • gnomAD v4.1 query for 10-87925512-G-A: absent; no allele frequency reported.
  • The corresponding non-cancer queries were also absent from gnomAD v2.1 non-cancer and gnomAD v3.1 non-cancer; no frequency was reported.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗

Not assessed · 13 · no assessment recorded

PS1 VCEPNot assessed: c.165-1G>C caused exon 3 skipping, but its pathogenic designation and comparable in silico score are unavailable for comparison with SpliceAI 0.976. Details ▾Hide ▴
Reasoning

The VCEP permits PS1 for a different variant at the same nucleotide position as a pathogenic splicing variant only when in silico models predict an impact equal to or greater than the known pathogenic variant. PTEN c.165-1G>C is reported to cause exon 3 skipping, but the available evidence does not establish its VCEP pathogenic designation or provide a comparable in silico score; the case variant's SpliceAI maximum delta is 0.976, so the required comparison cannot be completed.

VCEP rule
Same amino acid change as a previously established pathogenic variant regardless of nucleotide change OR different variant at same nucleotide position as a pathogenic splicing variant, where in silico models predict impact equal to or greater than the known pathogenic variant.
Evidence considered
  • CSPEC PS1 rule: same nucleotide position as a pathogenic splicing variant requires in silico impact equal to or greater than the known pathogenic variant.
  • PTEN c.165-1G>C was reported to cause exon 3 skipping and a predicted p.(Arg55Ser) plus p.(Phe56_Leu70del) consequence, but no comparator prediction score or VCEP pathogenic designation was provided.
  • The case variant is canonical splice acceptor c.165-1G>A with SpliceAI maximum delta 0.976.
Still missing
  • VCEP-established pathogenic designation for PTEN c.165-1G>C
  • Comparable in silico splice-impact score for PTEN c.165-1G>C
Sources
cspec ↗PMID:28677221 ↗
PS2 VCEPNot assessed: no documented germline de novo observation with confirmed maternity and paternity and no family history is available for this variant. Details ▾Hide ▴
Reasoning

No proband-level evidence documents a de novo occurrence of NM_000314.8:c.165-1G>A, confirmation of both maternity and paternity, or absence of family history. The available exact-variant paper evidence is a somatic tumor report, not a germline de novo observation, and therefore cannot satisfy the PTEN VCEP PS2 rule.

VCEP rule
De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history.
Evidence considered
  • No proband-level germline de novo observation, parental testing result, or family-history assessment is documented in the available case evidence.
  • PMID:34518631 reports PTEN c.165-1G>A in tumor tissue from case 7 and complete loss of PTEN immunoexpression, but does not establish a germline de novo observation or parental status.
Still missing
  • A germline proband observation with the variant and PTEN hamartoma tumor syndrome disease phenotype
  • Confirmation of both maternity and paternity
  • Documented absence of family history
Sources
cspec ↗PMID:34518631 ↗
PS3 VCEPNot assessed: no VCEP-qualifying functional assay for c.165-1G>A was available, and mmc2.xlsx contained no matching c.165-1G>A or p.? entry. Details ▾Hide ▴
Reasoning

The PTEN VCEP permits PS3 Strong for an RNA, mini-gene, or other assay showing an impact on splicing, PS3 Moderate for a high-confidence Mighell et al. 2018 phosphatase score <= -1.11, and PS3 Supporting for specified damaging functional assays. The exact variant NM_000314.8:c.165-1G>A (NP_000305.3:p.?) was not found in mmc2.xlsx under c.165-1G>A or p.?, and that VCEP file is indexed for missense variants. PMID:28677221 reports functional splicing effects for the different substitution c.165-1G>C, not this variant. PMID:34518631 reports tumor DNA detection and complete PTEN immunoexpression loss for this variant, but does not demonstrate aberrant splicing or provide a VCEP-qualifying functional assay with the required controls. Therefore PS3 cannot be evaluated from qualifying evidence in this case.

VCEP rule
PS3
Evidence considered
  • The PTEN VCEP PS3 rule allows RNA, mini-gene, or other assays showing impact on splicing; PS3 Moderate requires a high-confidence Mighell et al. 2018 phosphatase activity score <= -1.11.
  • mmc2.xlsx, searched in full text for c.165-1G>A and p.?: no matching row was found; the file is indexed for missense phosphatase assay data.
  • Characterization of cryptic splicing in germline PTEN intronic variants in Cowden syndrome (PMID:28677221), Results/exon-skipping paragraph: c.165-1G>C, not c.165-1G>A, caused exon 3 skipping in PTEN mRNA.
  • Sweat-gland carcinoma with neuroendocrine differentiation (PMID:34518631), Results/Next generation sequencing and Discussion: case 7 carried PTEN c.165-1G>A on tumor sequencing and had complete loss of PTEN immunoexpression; no splice assay was reported.
Still missing
  • No c.165-1G>A entry was found in the governing VCEP file mmc2.xlsx when searched for c.165-1G>A or p.?.
  • A variant-specific RNA, mini-gene, or other assay demonstrating splice impact, or another VCEP-qualifying functional assay with the required controls, is not available.
Sources
cspec ↗vcep_mmc2 ↗PMID:28677221 ↗PMID:34518631 ↗
PS4 VCEPNot assessed: no variant-specific case-control statistics or phenotype-specificity score is available to compare with the PTEN VCEP PS4 thresholds. Details ▾Hide ▴
Reasoning

The PTEN VCEP permits PS4 using either a sufficiently powered case-control study or phenotype-specificity scores across independent probands. No case-control odds ratio, p-value, confidence interval, Cleveland Clinic score, pediatric phenotype score, or independent-proband specificity total is available for this variant. The prospective Tan et al. cohort reports aggregate PTEN mutation categories but does not report c.165-1G>A or variant-specific phenotype data. The variant is absent from gnomAD, so the VCEP restriction that PS4 may not be applied if BS1 applies is not triggered by the available population evidence, but the PS4 evidence itself remains insufficient.

VCEP rule
**PTEN EP Commentary:** This criterion is unlikely to be used in this manner for a condition as rare as PHTS. However, if sufficiently powered, a case-control study finding an odds ratio >2 for a PHTS component phenotype with p\<0.05 and 95% confidence interval with lower limit >1.5, this criteria may be applied. However, this criterion may _not_ be applied in combination with PP4.  * Use 2: Patient’s phenotype or family history is highly specific for a disease with a single genetic etiology.  **PTEN EP Specifications:** This criterion may not be applied if BS1 applies.  Phenotype specificity scores are added across independent probands and calculated as follows:  Adults:  * 1 point per proband with Cleveland Clinic (CC) score ≥ 30 (Tan 2011) * 0.5 points per proband with CC score of 25-29. Children: * 1 point per proband with pediatric phenotype score ≥ 5 (please see supplementary information in manuscript for scoring rubric). * 0.5 points per proband with pediatric phenotype score of 4, but autism/developmental delay/intellectual disability may not contribute to the score. PS4\_Very Strong: Probands with specificity score ≥16. PS4: Probands with specificity score of 4-15.5. PS4\_Moderate: Probands with specificity score of 2-3.5. PS4\_Supporting: Proband(s) with specificity score of 1-1.5.
Evidence considered
  • ClinGen PTEN VCEP v3.2: PS4 may use a sufficiently powered case-control study or phenotype-specificity scores; available case evidence contains no variant-specific odds ratio, p-value, confidence interval, Cleveland Clinic score, pediatric phenotype score, or specificity total.
  • Tan et al. 2011 (PMID:21194675), prospective cohort of 3,042 probands: aggregate PTEN mutation spectrum included 19 splice-site donor and 9 splice-site acceptor mutations, but the paper does not mention PTEN c.165-1G>A or provide variant-specific clinical phenotype data.
  • gnomAD v2.1, gnomAD v4.1, and gnomAD-Canada v1.0: variant absent; no VCEP BS1 threshold comparison is applicable because no allele frequency was observed.
Still missing
  • Variant-specific case-control odds ratio, p-value, and 95% confidence interval are unavailable.
  • Cleveland Clinic or pediatric phenotype scores for independent probands are unavailable.
  • An independent-proband specificity score total is unavailable.
Sources
cspec ↗PMID:21194675 ↗
PM6 VCEPNot assessed: zero countable assumed de novo observations with disease and no family history are documented for this variant. Details ▾Hide ▴
Reasoning

No assumed de novo observations in affected probands are documented for NM_000314.8:c.165-1G>A, and the available evidence does not establish absence of family history or the number of assumed observations. The exact-variant tumor report does not provide the required germline de novo evidence.

VCEP rule
Assumed _de novo,_ but without confirmation of paternity and maternity, in proband with the disease and no family history.
Evidence considered
  • No countable assumed de novo proband observations, parental-status results, or family-history data are documented in the available case evidence.
  • PMID:34518631 reports the exact variant in FFPE tumor tissue, not as a germline presumed de novo observation.
Still missing
  • Countable assumed de novo proband observations
  • Disease phenotype for each proband
  • Absence of family history for each proband
  • Parental maternity and paternity status for each observation
Sources
cspec ↗PMID:34518631 ↗
PP1 VCEPNot assessed: no variant-specific affected-relative segregation or meiosis count is documented, so the 3-meiosis supporting threshold cannot be evaluated. Details ▾Hide ▴
Reasoning

No affected relatives with NM_000314.8:c.165-1G>A, phase-confirmed familial testing, or meiosis count is documented. PMID:9467011 describes segregation of other PTEN variants in some families but provides no variant-specific observation for c.165-1G>A, so it cannot establish PP1 for this variant.

VCEP rule
Co-segregation with disease in multiple affected family members, with 3 or 4 meioses observed.
Evidence considered
  • No variant-specific family segregation data, affected-relative testing results, or informative meiosis count are documented in the available case evidence.
  • Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, Table 1: the study reports other germline PTEN splice-site mutations and states that reported PTEN mutations segregated with disease where additional family members were available, but NM_000314.8:c.165-1G>A is not reported.
Still missing
  • Variant-specific testing of affected family members
  • Disease status and phenotype for each tested relative
  • Number of informative meioses
  • Evidence that the observations represent multiple affected family members
Sources
cspec ↗PMID:9467011 ↗
PP3 VCEPNot assessed: SpliceAI max delta 0.976 is available, but the PTEN rule requires concordance with the named VarSeak predictor, which is unavailable. Details ▾Hide ▴
Reasoning

The variant is a canonical splice-acceptor variant, so the VCEP's splicing path applies. That path requires concordance of SpliceAl and VarSeak. SpliceAI is available and predicts splice impact for NM_000314.8:c.165-1G>A, with DS_AG 0.862, DS_AL 0.976, DS_DG 0.0, DS_DL 0.084, and maximum delta score 0.976. No VarSeak result is available in the case evidence, so the required predictor concordance cannot be evaluated. The SpliceAI result is therefore not sufficient to apply PP3, and it is not reused for BP4 or BP7.

VCEP rule
Multiple lines of computational evidence support a deleterious effect on the gene or gene product. * Splicing variants: Concordance of SpliceAl and VarSeak * Missense variants: REVEL score > 0.7
Evidence considered
  • ClinGen PTEN VCEP PP3 rule: the splicing path requires concordance of SpliceAl and VarSeak.
  • SpliceAI Lookup for NM_000314.8:c.165-1G>A: DS_AG 0.862, DS_AL 0.976, DS_DG 0.0, DS_DL 0.084; maximum delta score 0.976.
  • No VarSeak result is present, so the VCEP-required predictor concordance is not evaluable.
Still missing
  • VarSeak prediction for NM_000314.8:c.165-1G>A is unavailable; concordance with SpliceAI cannot be evaluated.
Sources
cspec ↗spliceai ↗
BS2 Not assessed: no homozygous observation in a healthy or PHTS-unaffected individual, homozygote count, or clinical-status evidence is available. Details ▾Hide ▴
Reasoning

No observation of the variant in the homozygous state in a healthy or PHTS-unaffected individual is available. Absence from gnomAD does not establish a homozygous observation, and the available population records provide no homozygote count or individual-level clinical status.

Evidence considered
  • ClinGen PTEN VCEP specification v3.2, BS2 requires an observed homozygous state in a healthy or PHTS-unaffected individual and specifies different observation counts depending on confirmation.
  • gnomAD v2.1, gnomAD v4.1, gnomAD v2.1 non-cancer, and gnomAD v3.1 non-cancer all reported the variant as absent, with no homozygote count or individual-level phenotype information.
Still missing
  • A confirmed homozygous observation in a healthy or PHTS-unaffected individual, or two unconfirmed homozygous observations, is required by the VCEP rule.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
BS3 VCEPNot assessed: no VCEP-qualifying benign functional or splicing assay for c.165-1G>A was available, and mmc2.xlsx contained no matching c.165-1G>A or p.? entry. Details ▾Hide ▴
Reasoning

The PTEN VCEP requires an RNA, mini-gene, or other splicing assay demonstrating no splicing impact for intronic variants at BS3 Strong, or a functional study showing no damaging effect on protein function for BS3 Supporting; its Mighell-specific supporting path requires a high-confidence phosphatase activity score > 0. The exact variant NM_000314.8:c.165-1G>A (NP_000305.3:p.?) was not found in mmc2.xlsx under c.165-1G>A or p.?. The available variant-specific report describes complete loss, rather than absence, of PTEN immunoexpression in tumor tissue, and the comparator splicing paper concerns c.165-1G>C. No benign functional or splice assay meeting the VCEP rule is available, so BS3 cannot be evaluated.

VCEP rule
BS3
Evidence considered
  • The PTEN VCEP BS3 rule requires a no-impact splicing assay for intronic variants at Strong strength; BS3 Supporting requires a study showing no damaging effect, with Mighell et al. 2018 phosphatase activity > 0 as one specified path.
  • mmc2.xlsx, searched in full text for c.165-1G>A and p.?: no matching row was found; no phosphatase value or high-confidence flag is available for this variant.
  • Characterization of cryptic splicing in germline PTEN intronic variants in Cowden syndrome (PMID:28677221), Results/exon-skipping paragraph: the reported functional result concerns c.165-1G>C, not c.165-1G>A.
  • Sweat-gland carcinoma with neuroendocrine differentiation (PMID:34518631), Results/Next generation sequencing and Discussion: the variant was associated with complete loss of PTEN immunoexpression, which is not benign functional evidence.
Still missing
  • No c.165-1G>A entry was found in the governing VCEP file mmc2.xlsx when searched for c.165-1G>A or p.?.
  • A variant-specific RNA, mini-gene, or other assay demonstrating no splicing impact, or a VCEP-qualifying benign protein-function assay, is not available.
Sources
cspec ↗vcep_mmc2 ↗PMID:28677221 ↗PMID:34518631 ↗
BS4 VCEPNot assessed: no affected-family non-segregation observation is documented for this variant, so neither the one-family nor two-family threshold can be evaluated. Details ▾Hide ▴
Reasoning

No affected family members carrying or lacking NM_000314.8:c.165-1G>A are documented, and no family-level non-segregation result is available. Therefore, neither the one-family supporting rule nor the two-family strong rule can be evaluated.

VCEP rule
Lack of segregation in affected members of two or more families. ... Lack of segregation in affected members of one family.
Evidence considered
  • No affected-relative non-segregation result or family count is documented in the available case evidence.
  • The reviewed exact-variant and PTEN family literature does not provide a family-specific lack-of-segregation observation for NM_000314.8:c.165-1G>A.
Still missing
  • A family with affected members tested for the variant
  • Documented lack of variant segregation in one family for supporting evidence or two families for strong evidence
Sources
cspec ↗PMID:9467011 ↗PMID:34518631 ↗
BP2 VCEPNot assessed: no documented trans observation or at least three qualifying cis/phase-unknown observations with different pathogenic PTEN variants are available. Details ▾Hide ▴
Reasoning

BP2 is applicable at Supporting strength under the PTEN VCEP rule, but the available case evidence does not document the required allelic relationship: this variant observed in trans with a pathogenic or likely pathogenic PTEN variant, or at least three observations in cis and/or phase unknown with different pathogenic or likely pathogenic PTEN variants. The available ClinVar and literature records do not provide qualifying phase or co-occurrence observations for NM_000314.8:c.165-1G>A.

VCEP rule
Observed in trans with a pathogenic or likely pathogenic PTEN variant OR at least three observations in cis and/or phase unknown with different pathogenic/likely pathogenic PTEN variants.
Evidence considered
  • ClinGen PTEN Expert Panel specification v3.2, BP2 Supporting rule: "Observed in trans with a pathogenic or likely pathogenic PTEN variant OR at least three observations in cis and/or phase unknown with different pathogenic/likely pathogenic PTEN variants."
  • The available case evidence reports the target variant and general pathogenic classifications but contains no variant-specific trans, cis, phase-unknown, or affected-proband co-occurrence observation meeting the BP2 rule.
Still missing
  • Variant-specific co-occurrence data with another pathogenic or likely pathogenic PTEN variant
  • Phase determination for any reported co-occurrence
  • At least three cis or phase-unknown observations with different pathogenic or likely pathogenic PTEN variants if trans is not established
Sources
cspec ↗
BP4 VCEPNot assessed: SpliceAI max delta 0.976 predicts splice impact, but BP4 requires concordance with the named VarSeak predictor and that result is unavailable. Details ▾Hide ▴
Reasoning

The variant is a canonical splice-acceptor variant, so the VCEP's splicing path applies. That path requires concordance of SpliceAl and VarSeak to support no impact on the gene or gene product. SpliceAI is available and predicts splice impact, with DS_AG 0.862, DS_AL 0.976, DS_DG 0.0, DS_DL 0.084, and maximum delta score 0.976. No VarSeak result is available in the case evidence, so the required concordance cannot be evaluated. BP4 therefore cannot be assessed; the available SpliceAI result does not establish the VCEP's no-impact requirement and is not reused for PP3 or BP7.

VCEP rule
Multiple lines of computational evidence suggest no impact on gene or gene product.  * Splicing variants: Concordance of SpliceAl and VarSeak * Missense variants: REVEL scores < 0.5
Evidence considered
  • ClinGen PTEN VCEP BP4 rule: the splicing path requires concordance of SpliceAl and VarSeak.
  • SpliceAI Lookup for NM_000314.8:c.165-1G>A: DS_AG 0.862, DS_AL 0.976, DS_DG 0.0, DS_DL 0.084; maximum delta score 0.976, predicting possible splice impact.
  • No VarSeak result is present, so the VCEP-required predictor concordance is not evaluable.
Still missing
  • VarSeak prediction for NM_000314.8:c.165-1G>A is unavailable; concordance required by the VCEP cannot be evaluated.
Sources
cspec ↗spliceai ↗
BP5 VCEPNot assessed: no two cases with a highly penetrant alternate diagnosis and non-overlapping PTEN personal or family histories are documented. Details ▾Hide ▴
Reasoning

The VCEP requires at least two cases in which the variant is found with an alternate molecular basis for disease, and additionally requires that the other gene/disorder be highly penetrant and that the patient's personal or family history demonstrate no overlap between that disorder and PTEN. The available evidence provides no two qualifying cases, alternate highly penetrant molecular diagnosis, or non-overlapping personal/family histories.

VCEP rule
**PTEN EP Specifications:** At least two such cases are required for criteria to apply.  In addition, the other gene/disorder must be considered highly penetrant AND the patient’s personal/family history must demonstrate no overlap between the other gene and _PTEN_. Variant found in a case with an alternate molecular basis for disease. Other gene/disorder must be considered highly penetrant AND patient’s personal/family history must demonstrate no overlap between other gene and PTEN.
Evidence considered
  • ClinGen PTEN VCEP v3.2 requires at least two cases with an alternate molecular basis, a highly penetrant other gene/disorder, and personal/family histories showing no overlap with PTEN; none of these case-level data are available.
Still missing
  • At least two qualifying cases with an alternate molecular basis are unavailable.
  • Evidence that the alternate gene/disorder is highly penetrant is unavailable.
  • Personal and family histories demonstrating no phenotype overlap with PTEN are unavailable.
Sources
cspec ↗
Not applicable · 10· recorded as not applicable Show reasons ▾Hide reasons ▴
PM1 N/ANot applicable: PM1 names PTEN residues 90-94, 123-130, and 166-168, while c.165-1G>A is a splice-site variant with protein consequence p.?. Details ▾Hide ▴
Reasoning

The VCEP defines PM1 for residues in a mutational hotspot or critical functional domain, specifically catalytic motifs 90-94, 123-130, and 166-168. This variant is a canonical splice-site change, c.165-1G>A, with no resolved amino-acid residue (p.?), so it cannot be located in a residue-defined PM1 region. The authoritative vcep_materials.json domain_tables entry for PTEN is empty.

VCEP rule
Located in a mutational hot spot and/or critical and well-established functional domain. Defined to include residues in catalytic motifs: 90-94, 123-130, 166-168 (NP_ 000305.3)
Evidence considered
  • CSPEC PM1 defines the approved residue regions as catalytic motifs 90-94, 123-130, and 166-168 of NP_000305.3.
  • The case variant is canonical splice acceptor c.165-1G>A with protein consequence NP_000305.3:p.?, not a residue-resolved missense change.
  • vcep_materials.json domain_tables is empty for PTEN.
Sources
cspec ↗
PM3 VCEPNot applicable: the PTEN VCEP explicitly states that PM3 is not applicable to PTEN. Details ▾Hide ▴
Reasoning

PM3 is not applicable to PTEN under the ClinGen PTEN Expert Panel specification. The specification explicitly excludes this recessive-disease criterion, so phase, affected-proband observations, and other allelic evidence cannot activate PM3.

VCEP rule
This rule is not applicable to PTEN.
Evidence considered
  • ClinGen PTEN Expert Panel specification v3.2, PM3 entry: applicability is "Not applicable" and the instruction states, "This rule is not applicable to PTEN."
Sources
cspec ↗
PM4 N/ANot applicable: PM4 covers in-frame insertions/deletions or stop-loss protein length changes, whereas this variant is a canonical splice-site substitution. Details ▾Hide ▴
Reasoning

PM4 is not applicable because the VCEP rule is limited to protein length changes caused by in-frame insertions or deletions in a non-repeat region or by stop-loss variants, including in-frame changes affecting a catalytic motif or variants causing protein extension. This variant is a canonical splice-site substitution with an uncertain protein consequence (p.?), not an in-frame insertion, in-frame deletion, or stop-loss variant.

VCEP rule
Protein length changes due to in-frame deletions/insertions in a non-repeat region or stop-loss variants. Applies to in-frame insertions or deletions impacting at least one residue in a catalytic motif (see PM1), and variants causing protein extension.
Evidence considered
  • PTEN CSPEC PM4 rule: protein length changes due to in-frame deletions/insertions in a non-repeat region or stop-loss variants, including catalytic-motif in-frame changes and protein extensions.
  • Variant-level assessment: consequence class canonical_splice, protein consequence NP_000305.3:p.?, and no in-frame insertion/deletion or stop-loss classification.
Sources
cspec ↗pvs1_variant_assessment
PM5 N/ANot applicable: PM5 requires a missense change at an amino-acid residue, but c.165-1G>A is a canonical splice-site variant with protein consequence p.?. Details ▾Hide ▴
Reasoning

The VCEP PM5 rule requires a missense change at an amino-acid residue and comparison with a different pathogenic or likely pathogenic missense change using BLOSUM62. The case variant is canonical splice-site c.165-1G>A with protein consequence p.?, not a missense change at a defined amino-acid residue.

VCEP rule
Missense change at an amino acid residue where a different missense change determined to be pathogenic or likely pathogenic has been seen before. In addition, variant being interrogated must have BLOSUM62 score equal to or less than the known variant.
Evidence considered
  • CSPEC PM5 requires a missense change at an amino-acid residue and a different pathogenic or likely pathogenic missense change at that residue with BLOSUM62 comparison.
  • The case variant is classified as canonical_splice and has protein consequence NP_000305.3:p.?.
Sources
cspec ↗
PP2 N/ANot applicable: PP2 requires a missense variant, whereas c.165-1G>A is a canonical splice-site change. Details ▾Hide ▴
Reasoning

The VCEP PP2 rule applies to a missense variant in a gene with a low rate of benign missense variation and a common missense disease mechanism. The case variant is canonical splice-site c.165-1G>A, not a missense variant.

VCEP rule
Missense variant in a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.
Evidence considered
  • CSPEC PP2 applies to a missense variant in a gene with a low rate of benign missense variation and a common missense disease mechanism.
  • The case variant is canonical_splice c.165-1G>A with protein consequence NP_000305.3:p.?.
Sources
cspec ↗
PP4 VCEPNot applicable: the PTEN VCEP incorporates phenotype specificity into PS4 Use 2 rather than applying PP4. Details ▾Hide ▴
Reasoning

The PTEN VCEP explicitly marks PP4 as not applicable because phenotype specificity is incorporated into PS4 Use 2.

VCEP rule
PTEN EP Commentary: Phenotype specificity has been incorporated into the rule specifications for PS4 Use 2.
Evidence considered
  • ClinGen PTEN VCEP v3.2 marks PP4 as not applicable and states that phenotype specificity has been incorporated into PS4 Use 2.
Sources
cspec ↗
BP1 VCEPNot applicable: the PTEN VCEP explicitly marks BP1 as Not Applicable. Details ▾Hide ▴
Reasoning

The PTEN VCEP marks BP1 as Not Applicable. No BP1 evidence is therefore evaluated or assigned.

VCEP rule
Not Applicable
Evidence considered
  • CSPEC BP1 applicability is explicitly recorded as Not Applicable.
Sources
cspec ↗
BP3 VCEPNot applicable: the PTEN VCEP explicitly designates BP3 as Not Applicable for this framework. Details ▾Hide ▴
Reasoning

The PTEN VCEP CSPEC entry explicitly marks BP3 as Not Applicable. BP3 therefore cannot be applied to this variant under the governing PTEN framework, regardless of the splice-site consequence or repeat-region context.

VCEP rule
Not Applicable
Evidence considered
  • PTEN CSPEC criterion entry for BP3: applicability is explicitly recorded as Not Applicable.
Sources
cspec ↗
BP6 VCEPNot applicable: the PTEN VCEP prohibits use of BP6, regardless of whether a reputable benign source is available. Details ▾Hide ▴
Reasoning

The PTEN VCEP explicitly states that BP6 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee; therefore a reputable benign source cannot establish BP6 under this VCEP.

VCEP rule
This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
Evidence considered
  • ClinGen PTEN VCEP v3.2 marks BP6 as not applicable and prohibits its use.
Sources
cspec ↗
BP7 N/ANot applicable: c.165-1G>A is a canonical splice-acceptor variant at -1, outside BP7's synonymous or intronic at-or-beyond +7/-21 scope. Details ▾Hide ▴
Reasoning

BP7 is limited by the VCEP to synonymous variants or intronic variants at or beyond +7/-21. NM_000314.8:c.165-1G>A is a canonical intronic splice-acceptor variant at position -1, outside that scope. BP7 is therefore not applicable, regardless of the available splice prediction.

VCEP rule
A synonymous (silent) or intronic variant at or beyond +7/-21 for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice.
Evidence considered
  • ClinGen PTEN VCEP BP7 scope covers synonymous variants or intronic variants at or beyond +7/-21; c.165-1G>A is a canonical -1 splice-acceptor variant.
Sources
cspec ↗

Identifiers

Gene
PTEN
Transcript
NM_000314.8
Coding (HGVS c.)
NM_000314.8:c.165-1G>A
Protein (HGVS p.)
NP_000305.3:p.?
GRCh38
chr10:87925512 G>A
GRCh37
chr10:89685269 G>A
Location and type
Intron 2 · canonical splice
ClinVar
187590
COSMIC
COSV64292036

Gene diagram

Every interpreted variant in PTEN, mapped onto the exon structure of NM_000314.8. Select a row to find it on the plot.

PTENNM_000314.8
Fetching transcript structure from UCSC…
gnomAD v4.1 Allele count data not recorded
gnomAD v2.1 Allele count data not recorded
gnomAD-Canada v1.0 Allele count data not recorded

Statements

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat +1 bp
0.976
SpliceAI acceptor gainat +2 bp
0.862
SpliceAI donor lossat +49 bp
0.084
SpliceAI donor gainat +378 bp
0.000
Pangolin splice lossmagnitude shown
-0.858
Pangolin splice gain
0.823

Other predictors

REVEL
Not available
BayesDel
0.387

How the predictions were used

PP3 VCEPNot assessed: SpliceAI max delta 0.976 is available, but the PTEN rule requires concordance with the named VarSeak predictor, which is unavailable. Details ▾Hide ▴
Reasoning

The variant is a canonical splice-acceptor variant, so the VCEP's splicing path applies. That path requires concordance of SpliceAl and VarSeak. SpliceAI is available and predicts splice impact for NM_000314.8:c.165-1G>A, with DS_AG 0.862, DS_AL 0.976, DS_DG 0.0, DS_DL 0.084, and maximum delta score 0.976. No VarSeak result is available in the case evidence, so the required predictor concordance cannot be evaluated. The SpliceAI result is therefore not sufficient to apply PP3, and it is not reused for BP4 or BP7.

VCEP rule
Multiple lines of computational evidence support a deleterious effect on the gene or gene product. * Splicing variants: Concordance of SpliceAl and VarSeak * Missense variants: REVEL score > 0.7
Evidence considered
  • ClinGen PTEN VCEP PP3 rule: the splicing path requires concordance of SpliceAl and VarSeak.
  • SpliceAI Lookup for NM_000314.8:c.165-1G>A: DS_AG 0.862, DS_AL 0.976, DS_DG 0.0, DS_DL 0.084; maximum delta score 0.976.
  • No VarSeak result is present, so the VCEP-required predictor concordance is not evaluable.
Still missing
  • VarSeak prediction for NM_000314.8:c.165-1G>A is unavailable; concordance with SpliceAI cannot be evaluated.
Sources
cspec ↗spliceai ↗
BP4 VCEPNot assessed: SpliceAI max delta 0.976 predicts splice impact, but BP4 requires concordance with the named VarSeak predictor and that result is unavailable. Details ▾Hide ▴
Reasoning

The variant is a canonical splice-acceptor variant, so the VCEP's splicing path applies. That path requires concordance of SpliceAl and VarSeak to support no impact on the gene or gene product. SpliceAI is available and predicts splice impact, with DS_AG 0.862, DS_AL 0.976, DS_DG 0.0, DS_DL 0.084, and maximum delta score 0.976. No VarSeak result is available in the case evidence, so the required concordance cannot be evaluated. BP4 therefore cannot be assessed; the available SpliceAI result does not establish the VCEP's no-impact requirement and is not reused for PP3 or BP7.

VCEP rule
Multiple lines of computational evidence suggest no impact on gene or gene product.  * Splicing variants: Concordance of SpliceAl and VarSeak * Missense variants: REVEL scores < 0.5
Evidence considered
  • ClinGen PTEN VCEP BP4 rule: the splicing path requires concordance of SpliceAl and VarSeak.
  • SpliceAI Lookup for NM_000314.8:c.165-1G>A: DS_AG 0.862, DS_AL 0.976, DS_DG 0.0, DS_DL 0.084; maximum delta score 0.976, predicting possible splice impact.
  • No VarSeak result is present, so the VCEP-required predictor concordance is not evaluable.
Still missing
  • VarSeak prediction for NM_000314.8:c.165-1G>A is unavailable; concordance required by the VCEP cannot be evaluated.
Sources
cspec ↗spliceai ↗
BP7 N/ANot applicable: c.165-1G>A is a canonical splice-acceptor variant at -1, outside BP7's synonymous or intronic at-or-beyond +7/-21 scope. Details ▾Hide ▴
Reasoning

BP7 is limited by the VCEP to synonymous variants or intronic variants at or beyond +7/-21. NM_000314.8:c.165-1G>A is a canonical intronic splice-acceptor variant at position -1, outside that scope. BP7 is therefore not applicable, regardless of the available splice prediction.

VCEP rule
A synonymous (silent) or intronic variant at or beyond +7/-21 for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice.
Evidence considered
  • ClinGen PTEN VCEP BP7 scope covers synonymous variants or intronic variants at or beyond +7/-21; c.165-1G>A is a canonical -1 splice-acceptor variant.
Sources
cspec ↗

Statement

In silico

SpliceAI predicts possible splice impact for this variant (max delta score = 0.98). BayesDel score = 0.387045.

8 paper records listed. No publication is explicitly linked to an applied criterion in the recorded metadata.

Recorded publications

  • Splicing in action: assessing disease causing sequence changes.
    Baralle D et al. · 2005
    No paper-specific finding is recorded.
    PMID 16199547 ↗
  • Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.
    No paper-specific finding is recorded.
    PMID 25741868 ↗
  • A Standardized DNA Variant Scoring System for Pathogenicity Assessments in Mendelian Disorders.
    No paper-specific finding is recorded.
    PMID 26467025 ↗
  • Characterization of cryptic splicing in germline PTEN intronic variants in Cowden syndrome.
    Chen HJ et al. · 2017
    The paper does not explicitly mention PTEN c.165-1G>A. It reports that the different substitution at the same splice-acceptor position, PTEN c.165-1G>C, caused exon 3 skipping in PTEN mRNA and produced a predicted p.(Arg55Ser) plus p.(Phe56_Leu70del) consequence.
    Does not name this variant
    PMID 28677221 ↗
    Quoted passage
    The intron 2, 3′ splice-acceptor mutation c.165-1G>C causes exon 3 skipping in the PTEN mRNA transcript, and alters the PTEN protein coding sequence dramatically, changing Arg55 to serine and deleting 15 amino acids from Phe56 to Leu70.

    Results, exon-skipping paragraph; Table 1

  • Gene-specific criteria for PTEN variant curation: Recommendations from the ClinGen PTEN Expert Panel.
    Mester JL et al. · 2018
    No paper-specific finding is recorded.
    PMID 30311380 ↗
  • Sweat-gland carcinoma with neuroendocrine differentiation (SCAND): a clinicopathologic study of 13 cases with genetic analysis.
    Goto K et al. · 2022
    The paper explicitly reports PTEN c.165-1G>A in case 7 from targeted sequencing of tumor tissue and complete loss of PTEN immunoexpression, but it does not report germline inheritance, parental testing, family segregation, or non-segregation.
    Names this variant
    PMID 34518631 ↗
    Quoted passage
    A total of nine mutations, including 1 mutation of PTEN, 2 mutations of PIK3CA, and six mutations of FLT3, were revealed in case 7, but only PTEN c.165-1G>A splice site mutation was evaluated as a pathogenic one with reference to COSMIC and ClinVar.

    Results, “Next generation sequencing”; Discussion, paragraph beginning “PTEN c.165-1G>A splice site mutation detected in case 7”

  • Mutation spectrum and genotype-phenotype analyses in Cowden disease and Bannayan-Zonana syndrome, two hamartoma syndromes with germline PTEN mutation.
    Marsh DJ et al. · 1998
    The exact PTEN variant c.165-1G>A is not explicitly reported. The study reports germline PTEN splice-site mutations among Cowden disease and Bannayan-Zonana syndrome families and describes segregation of reported PTEN mutations with disease when additional family members were available, but it provides no variant-specific segregation or non-segregation observation for c.165-1G>A.
    Does not name this variant
    PMID 9467011 ↗
    Quoted passage
    Of the 30 CD PTEN mutations identified, 10 (33%) were nonsense point mutations, six (20%) were missense point mutations, six (20%) were insertions, four (13%) were deletions, three (10%) were splice site mutations and one (3%) was a deletion/insertion mutation

    Results, PTEN mutation analysis in CD and BZS; Table 1

  • A clinical scoring system for selection of patients for PTEN mutation testing is proposed on the basis of a prospective study of 3042 probands.
    Tan MH et al. · 2011
    This prospective study examined 3,042 probands undergoing PTEN mutation testing and identified 290 individuals with pathogenic germline PTEN mutations, including splice-site donor and acceptor mutations. In patient-derived lymphoblasts from PTEN-mutant individuals, PTEN protein expression was decreased and phospho-AKT1 expression was relatively increased. The paper does not explicitly mention PTEN c.165-1G>A or provide variant-specific functional, clinical, segregation, or population-frequency data for it.
    Does not name this variant
    PMID 21194675 ↗
    Quoted passage
    In total, 85 (29%) missense mutations, 92 (32%) nonsense mutations, 42 (14%) small deletions, 24 (8%) small insertions, 3 (1%) indels, 8 (3%) large deletions, 19 (7%) splice-site donor mutations, 9 (3%) splice-site acceptor mutations, and 8 (3%) promoter mutations were found.

    Results, ‘PTEN Mutation Spectrum in Patients’; Results, ‘PTEN Genotype, Clinical Score, and Downstream Pathway Proteins’

Screenshots represent source records captured during evidence collection. Select one to view the recorded source content.

gnomAD v4.1 Captured gnomAD v4.1 source record Open source ↗
gnomAD v2.1 Captured gnomAD v2.1 source record Open source ↗
SpliceAI Lookup Recorded maximum delta 0.976 Open source ↗
ClinVar 5 Pathogenic · 1 pathogenic Open source ↗
COSMIC Captured COSMIC source record Open source ↗
ClinGen CSpec Captured ClinGen CSpec source record Open source ↗

All source links

Statements for reports

The evidence statements recorded by the interpretation pipeline. They have not been reinterpreted by the page.

gnomAD v4.1

Absent from gnomAD v4.1.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Absent from gnomAD-Canada v1.0.

ClinVar

This variant has been reported in ClinVar as Pathogenic (5 clinical laboratories) and as pathogenic (1 clinical laboratory) and as Likely Pathogenic by Clingen PTEN Variant Curation Expert Panel, Clingen (expert panel). (ClinVarID = 187590)

In silico

SpliceAI predicts possible splice impact for this variant (max delta score = 0.98). BayesDel score = 0.387045.

Somatic

This variant has previously been reported in somatic cancers (COSMIC; COSV64292036, n = 9 times).