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PIK3CAc.2107_2121dupUncertain significance
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Variant interpretation report

PIK3CA c.2107_2121dup, p.Asn703_Glu707dup

NM_006218.4:c.2107_2121dup NP_006209.2:p.(Asn703_Glu707dup) In frame indel unknown · exon 14 View identifiers
Classification
Uncertain significance

Variant description:

The PIK3CA NM_006218.4:c.2107_2121dup (NP_006209.2:p.(Asn703_Glu707dup)) in-frame duplication variant has not previously been reported in somatic cancers (COSMIC). Based on available guidelines, this variant is considered to be a Variant of Uncertain Significance (VUS).

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

Uncertain.The recorded classification is uncertain significance.

In plain language

Gene-level background from the recorded interpretation.

About PIK3CA

PIK3CA encodes the p110α catalytic subunit of phosphoinositide 3-kinase (PI3K), an enzyme that converts the membrane lipid PIP2 into PIP3, thereby activating signaling cascades such as the AKT-mTOR pathway that promote cell survival, proliferation, growth, and motility. It is among the most commonly mutated genes in cancer, and aberrant activation of PI3K signaling is a driving event in tumor development, with the gene implicated in cancers including cervical cancer. Because this pathway is central to tumor growth, it is a major target of cancer therapies, although drug-induced pathway activation can also contribute to treatment resistance.

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 PIK3CA VCEP v1.1. 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: 0 Benign evidence criteria: 0
Pathogenic criteria applied · 0

No pathogenic criterion marked as applied in the recorded assessment.

Benign criteria applied · 0

No benign criterion marked as applied in the recorded assessment.

Recorded classification: Uncertain significance

VUS: no adjudicated criteria are applied, so the ACMG/AMP 2015 Table 5 thresholds for pathogenic, likely pathogenic, benign, or likely benign are not met.

02The sources

Evidence at a glance

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

gnomAD v4.1
gnomAD v2.1
Population frequency
Not recorded

gnomAD v4.1 allele counts were not recorded for this variant.

gnomAD v2.1

Absent from gnomAD v2.1.

gnomAD-Canada

Not available in gnomAD-Canada v1.0.

No listed criterion applied
gnomAD v4.1 ↗gnomAD v2.1 ↗gnomAD-Canada ↗
SpliceAI score
0.012 maximum delta

Recorded SpliceAI maximum delta score: 0.012. Refer to the recorded PP3/BP4 rationale for interpretation.

No listed criterion applied SpliceAI ↗
No screenshot for this evidence
ClinVar submissions
Not recorded

A ClinVar laboratory submission summary was not recorded.

Context only ClinVar ↗
Functional evidence
Statement recorded

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PIK3CA, the catalytic subunit of PI3-kinase, is frequently mutated in a diverse range of cancers including breast, endometrial and cervical cancers.

No listed criterion applied OncoKB ↗
COSMIC
Cancer Hotspots
Somatic evidence
No matching record reported

This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.

Context only
COSMIC ↗Cancer Hotspots ↗
For specialists

Technical detail

ACMG/AMP criteria under ClinGen PIK3CA VCEP v1.1, with the data and sources behind each one.

28 criteria with recorded statuses: 0 met · 5 not met · 6 not assessed · 17 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

Not met · 5 · evaluated, threshold not reached

PS4 VCEPNot met: no affected carrier or case-control observation was identified, so the VCEP Table 2A phenotype score is 0 points. Details ▾Hide ▴
Reasoning

The VCEP requires PS4 phenotype points under Table 2A and states that phenotype criteria can only be used if the variant meets PM2. The variant is absent from gnomAD v2.1 and v4.1, satisfying the available PM2 prerequisite, but no affected individual carrying NM_006218.4:c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was identified: literature_pass.json contains zero PMIDs, paper_extracts.json is empty, and the governing VCEP full-text file contains no notation of this variant. Therefore no Table 2A phenotype points can be assigned and PS4 is not met. No case-control counts or odds ratio are available to calculate.

VCEP rule
Points are assigned for phenotype according to (Table 2A). Phenotype criteria can only be used if the variant is absent from controls (PM2). Strength of evidence is determined by points according to (Table 2B). PS4 = 3.5-15.75 points
Evidence considered
  • ClinGen Brain Malformations VCEP Table 2A/Table 2B rule: phenotype points are required for PS4, and the variant must first meet PM2.
  • The case evidence reports the variant absent from gnomAD v2.1 and gnomAD v4.1.
  • literature_pass.json reports total_pmids: 0; paper_extracts.json is empty, so no variant-specific affected-patient publication or case-control comparison was available.
  • The governing file clingen_brainmalform_acmg_specifications_v1_1.pdf was searched under all three requested variant notations and returned no matching entry.
Still missing
  • No case-control counts, unaffected controls, or affected-case series were available for this variant; therefore an odds ratio and 95% confidence interval cannot be calculated.
  • The governing file clingen_brainmalform_acmg_specifications_v1_1.pdf was searched for c.2107_2121dup, p.Asn703_Glu707dup, and p.N703_E707dup; no entry was found.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
PM1 VCEPNot met: p.Asn703_Glu707dup spans residues 703-707, outside all approved PIK3CA domains (31-108, 173-292, 322-483, and 797-1068). Details ▾Hide ▴
Reasoning

The VCEP limits PM1_Supporting to variants located in an exon within an approved Table 4 functional domain and excludes recurrent gain-of-function residues from PM1. The authoritative PIK3CA domain table lists the kinase domains as residues 322-483 and 797-1068, the Kinase Ras-binding domain as 173-292, and the adaptor binding domain as 31-108. The variant is NP_006209.2:p.(Asn703_Glu707dup), spanning residues 703-707; it is outside every approved PIK3CA domain. The VCEP file search found no exact entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.

VCEP rule
A supporting point may be awarded if the variant of interest is located in an exon within one of the below approved functional domains Table 4. Please note that specific residues subject to recurrent gain-of-function mutations are not covered by this criterion; these are instead accounted for by PS4.
Evidence considered
  • ClinGen Brain Malformations VCEP specification v1.1, Table 4, PIK3CA row: approved domains are Kinase Ras-binding domain AA 173-292, kinase domains AA 322-483 and AA 797-1068, and adaptor binding domain (PI3K ABD) AA 31-108.
  • Case normalization: NM_006218.4:c.2107_2121dup gives NP_006209.2:p.(Asn703_Glu707dup), spanning amino-acid residues 703-707; this interval does not overlap any approved PIK3CA Table 4 domain.
  • The VCEP search returned no exact match for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup in the governing full-text file.
Still missing
  • No exact entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt; the domain-table rule was still evaluable.
Sources
vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
BA1 VCEPNot met: the variant was absent from all queried gnomAD datasets, rather than exceeding the VCEP BA1 allele-frequency threshold of >0.0926%. Details ▾Hide ▴
Reasoning

The governing VCEP assigns BA1 when allele frequency is >0.0926%. The variant was absent from gnomAD v2.1, gnomAD v4.1, gnomAD v2.1 non-cancer, and gnomAD v3.1 non-cancer, so no observed allele frequency exceeds the BA1 threshold. The variant was not found under c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup in the governing VCEP full-text file.

VCEP rule
Allele frequency (>0.0926%). An allele frequency (>0.0926%) was approved.
Evidence considered
  • ClinGen Brain Malformations VCEP BA1 rule: allele frequency >0.0926%.
  • gnomAD v2.1 all-comers query for 3-178938863-T-TGAATAGGCAAGTCGA: absent.
  • gnomAD v4.1 all-comers query for chr3-179221075-T-TGAATAGGCAAGTCGA: absent.
  • The case evidence also records absence in gnomAD v2.1 non-cancer and gnomAD v3.1 non-cancer subsets.
Still missing
  • No variant-specific entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
BS1 VCEPNot met: the variant was absent from all queried gnomAD datasets, rather than exceeding the VCEP BS1 allele-frequency threshold of >0.0185%. Details ▾Hide ▴
Reasoning

The governing VCEP assigns BS1 when allele frequency is >0.0185%. The variant was absent from gnomAD v2.1, gnomAD v4.1, gnomAD v2.1 non-cancer, and gnomAD v3.1 non-cancer, so no observed allele frequency exceeds the BS1 threshold. The variant was not found under c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup in the governing VCEP full-text file.

VCEP rule
Allele frequency (>0.0185%). An allele frequency (>0.0185%) was approved. (Supplemental Table 3).
Evidence considered
  • ClinGen Brain Malformations VCEP BS1 rule: allele frequency >0.0185%.
  • gnomAD v2.1 all-comers query for 3-178938863-T-TGAATAGGCAAGTCGA: absent.
  • gnomAD v4.1 all-comers query for chr3-179221075-T-TGAATAGGCAAGTCGA: absent.
  • The case evidence also records absence in gnomAD v2.1 non-cancer and gnomAD v3.1 non-cancer subsets.
Still missing
  • No variant-specific entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
BS2 VCEPNot met: gnomAD reports no occurrence of the variant, and no evidence shows the VCEP-required three homozygotes or three well-phenotyped family heterozygotes. Details ▾Hide ▴
Reasoning

The governing VCEP requires at least three homozygotes in gnomAD or at least three heterozygous observations in well-phenotyped family members. The variant is absent from the queried gnomAD datasets, providing no gnomAD homozygotes, and the available case evidence contains no well-phenotyped family-member observations. The variant was not found under c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup in the governing VCEP full-text file.

VCEP rule
Award BS2 if ≥3 homozygotes present in gnomAD or ≥3 heterozygous in well phenotyped family members. Clinical laboratories are encouraged to accumulate more than 2 (≥3) instances of well phenotyped family members before applying this strong criterion. To be considered for this point, the variant should be either germline (most common), or somatic in a relevant tissue. Homozygous occurrences in gnomAD or ExAC can also be counted for this point (≥3).
Evidence considered
  • ClinGen Brain Malformations VCEP BS2 rule requires at least 3 homozygotes in gnomAD or at least 3 heterozygotes in well-phenotyped family members.
  • gnomAD v2.1 and v4.1 all-comers queries were absent; the case evidence also records absence in the v2.1 non-cancer and v3.1 non-cancer subsets.
  • No family-member observations or phenotype documentation were present in the available evidence.
Still missing
  • No variant-specific entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
  • No well-phenotyped family-member segregation data were available.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗

Not assessed · 6 · no assessment recorded

PS2 VCEPNot assessed: no proband, parental-testing, confirmed maternity/paternity, allele-fraction, or cross-tissue evidence is available to evaluate the VCEP PS2 criteria. Details ▾Hide ▴
Reasoning

The VCEP provides PS2 criteria for de novo and tissue-mosaic evidence, but the available case evidence contains no proband phenotype/genotype record, parental testing results, confirmed maternity or paternity, allele fractions, or affected-versus-unaffected tissue comparison. Therefore PS2 cannot be assessed.

VCEP rule
Award the PS2_Strong point if Criteria 1 AND Criteria 2 are fulfilled. ... Criteria 1. The variant is present at a detectable allele fraction but is absent from parental samples with confirmed maternity and paternity. ... Criteria 2. The variant is present at a detectable allele fraction in an affected tissue sample but is absent from or detected at a lower allelic fraction in another tissue (e.g. if present in 5% of brain tissue but absent from the blood or skin this point can be awarded). ... Award the PS2_Moderate point if Criteria 1 is fulfilled, OR if parents are not available but Criteria 2 is fulfilled.
Evidence considered
  • ClinGen Brain Malformations VCEP specification v1.1, PS2 entry: PS2_Strong requires both parental absence with confirmed maternity and paternity and an affected-tissue versus another-tissue allele-fraction comparison; PS2_Moderate permits Criteria 1 alone or Criteria 2 when parents are unavailable.
  • The case evidence contains no proband, parental, maternity/paternity, allele-fraction, or tissue-comparison findings for NM_006218.4:c.2107_2121dup.
Still missing
  • No proband-level disease and variant observation details are available.
  • No parental samples or confirmed maternity and paternity results are available.
  • No detectable allele-fraction measurements or affected-versus-other-tissue comparison are available.
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
PS3 VCEPNot assessed: no variant-specific functional assay, controls, or validated measurements are available to apply the VCEP PS3 acceptability requirements. Details ▾Hide ▴
Reasoning

The Brain Malformations VCEP requires PS3 functional evidence to meet the acceptability criteria in PMID: 31892348 and the BMVCEP quality metrics and minimum validation controls in Supplementary Document 1. The available case evidence contains no functional assay, assay result, validation controls, or PMID-linked functional publication for NM_006218.4:c.2107_2121dup (p.Asn703_Glu707dup; p.N703_E707dup). The governing VCEP full-text file was searched for all three variant notations and contained no matching entry. Therefore PS3 cannot be evaluated.

VCEP rule
Brain Malformation Recommendation: Award PS3 if the functional assay meets the acceptability criteria delimited in (PMID: 31892348) with specifications added by the BMVCEP. Quality metrics and minimum validation controls required can be found in Supplementary Document 1.
Evidence considered
  • ClinGen Brain Malformations VCEP specification v1.1: PS3 requires the functional assay to meet PMID: 31892348 acceptability criteria plus BMVCEP quality metrics and minimum validation controls in Supplementary Document 1.
  • The case evidence records no literature PMIDs and no variant-specific functional assay evidence for NM_006218.4:c.2107_2121dup.
  • The governing full-text VCEP file was searched under c.2107_2121dup, p.Asn703_Glu707dup, and p.N703_E707dup; no matching variant entry was found.
Still missing
  • No variant-specific functional assay results or assay-control details are available.
  • No PMID-linked functional publication is available for this variant.
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
PM2 VCEPNot assessed: the variant is absent from gnomAD, but no available dataset identifies an ethnically matched cohort as required by the VCEP PM2 rule. Details ▾Hide ▴
Reasoning

The governing VCEP permits PM2 at Supporting strength for a variant absent or rare from controls in an ethnically-matched cohort population sample (≥1). The variant was absent from gnomAD v2.1, gnomAD v4.1, gnomAD v2.1 non-cancer, and gnomAD v3.1 non-cancer, but the available records do not identify an ethnically matched cohort for this case. Therefore the absence evidence is insufficient to verify the VCEP's ancestry-matching requirement, and PM2 is not assessed.

VCEP rule
Absent/rare from controls in an ethnically-matched cohort population sample ( ≥1).
Evidence considered
  • ClinGen Brain Malformations VCEP PM2 rule: absent/rare from controls in an ethnically-matched cohort population sample (≥1).
  • gnomAD v2.1 and v4.1 all-comers queries were absent; the case evidence also records absence in the v2.1 non-cancer and v3.1 non-cancer subsets.
  • The available gnomAD records do not establish that the queried population is ethnically matched to the case.
Still missing
  • No variant-specific entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
  • The ancestry of the case and an explicitly ethnically matched control cohort were not available.
Sources
cspec ↗gnomad_v2 ↗gnomad_v4 ↗
BS3 VCEPNot assessed: no variant-specific benign functional study with the VCEP-required controls and quality metrics is available for BS3. Details ▾Hide ▴
Reasoning

The Brain Malformations VCEP defines BS3 using well-established in vitro or in vivo functional studies showing no damaging effect, with SVI/BMVCEP quality metrics and minimum validation controls. No variant-specific benign functional assay, assay controls, or validated measurements are available for NM_006218.4:c.2107_2121dup (p.Asn703_Glu707dup; p.N703_E707dup). The governing VCEP full-text file was searched for all three variant notations and contained no matching entry. Therefore BS3 cannot be evaluated.

VCEP rule
Well-established in vitro or in vivo functional studies shows no damaging effect on protein function. Brain Malformation Recommendation: Follow recommendations set forth by the SVI in conjunction with specifications added by the Brain Malformation Group for quality metrics and minimum validation controls required (PMID: 31892348) (Supplementary Document 1)
Evidence considered
  • ClinGen Brain Malformations VCEP specification v1.1: BS3 requires well-established functional studies showing no damaging effect and the SVI/BMVCEP quality metrics and minimum validation controls.
  • The available case evidence contains no variant-specific benign functional assay, assay-control data, or PMID-linked functional publication.
  • The governing full-text VCEP file was searched under c.2107_2121dup, p.Asn703_Glu707dup, and p.N703_E707dup; no matching variant entry was found.
Still missing
  • No variant-specific benign functional assay results or assay-control details are available.
  • No validated in vitro or in vivo measurement showing no damaging effect is available.
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
BP2 VCEPNot assessed: no cis/trans observation with a known pathogenic PIK3CA variant is documented. Details ▾Hide ▴
Reasoning

The governing VCEP rule permits BP2 only when the variant is observed in cis or trans with a known pathogenic variant in the same gene. No such cis/trans observation, phase result, or pathogenic PIK3CA partner variant is documented in the available case evidence. The variant was not found under c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup in the governing full-text file, so BP2 cannot be evaluated from this record.

VCEP rule
Observed in cis or trans with a known pathogenic variant in the same gene.
Evidence considered
  • ClinGen Brain Malformations VCEP BP2 rule: observed in cis or trans with a known pathogenic variant in the same gene.
  • The case bundle contains no affected-proband phase result, parental or offspring testing result, cis/trans observation, or known pathogenic PIK3CA partner variant.
  • The governing full-text file was searched for c.2107_2121dup, p.Asn703_Glu707dup, and p.N703_E707dup; no variant-specific entry was found.
Still missing
  • No cis/trans phase data or known pathogenic PIK3CA partner variant is available for this case.
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
BP5 ACMG_2015Not assessed: no case record establishes that the variant occurred with an alternate molecular basis for disease in a different gene. Details ▾Hide ▴
Reasoning

The VCEP marks BP5 as applicable as originally described and specifies that the variant must be found in a case with an alternate molecular basis for disease in a different gene. The available case materials contain no affected-case report, alternate diagnosis, or other evidence establishing that this variant occurred in such a case. Because the required case context is unavailable, BP5 cannot be assessed rather than being inferred from the absence of a record.

Rule
Variant found in a case with an alternate molecular basis for disease.
Evidence considered
  • The VCEP BP5 entry is applicable as originally described and defines the finding as a variant in a case with an alternate molecular basis for disease.
  • The VCEP's Brain Malformation Recommendation specifies an alternate molecular basis in a different gene; no such case-level evidence is present in the available materials.
Still missing
  • A documented affected case with this variant and an alternate molecular basis for disease in a different gene is required to assess BP5.
Sources
cspec ↗
Not applicable · 17· recorded as not applicable Show reasons ▾Hide reasons ▴
PVS1 VCEPNot applicable: the VCEP excludes PVS1 for this gene. Details ▾Hide ▴
Reasoning

The ClinGen Brain Malformations Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1 marks PVS1 as not applicable. The VCEP states: "LOF and/or haploinsufficiency have not been clearly identified as disease mechanisms underlying brain malformations related to these genes, so in general this rule is not applicable. The disease mechanism for these genes is gain of function (GOF)." NM_006218.4:c.2107_2121dup in PIK3CA is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_006209.2:p.(Asn703_Glu707dup). This determination was made deterministically from the VCEP criteria specification, prior to LLM adjudication.

VCEP rule
deterministic_prefilter: vcep_not_applicable
Evidence considered
  • Deterministic consequence classification: in_frame_indel_unknown (prefetch.json normalized protein consequence)
  • VCEP criterion policy: vcep_not_applicable
Sources
cspec ↗
PS1 N/ANot applicable: PS1 requires a missense variant, and this is an in-frame indel. Details ▾Hide ▴
Reasoning

PS1 (Richards et al. 2015, PMID:25741868) requires the same amino acid change as a previously established pathogenic variant, evaluated regardless of the underlying nucleotide change. NM_006218.4:c.2107_2121dup in PIK3CA is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_006209.2:p.(Asn703_Glu707dup). As a result, no altered amino acid exists at this position to compare against any previously established pathogenic missense variant, so PS1's structural prerequisite is not met by this variant class. The ClinGen Brain Malformations Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1 applies PS1 as originally described in ACMG/AMP 2015, so the original definition governs. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.

Rule
deterministic_prefilter: requires_missense
Evidence considered
  • Deterministic consequence classification: in_frame_indel_unknown (prefetch.json normalized protein consequence)
  • VCEP criterion policy: vcep_unchanged
Sources
generic_acmg_combination_rulescspec ↗
PM3 VCEPNot applicable: the VCEP states PM3 is not applicable because disease-causing variants are heterozygous. Details ▾Hide ▴
Reasoning

The ClinGen Brain Malformations VCEP specifies that PM3 is not applicable because disease-causing variants in this framework are heterozygous. The case evidence contains no phase or recessive affected-proband observation that could override this VCEP applicability decision. Searches of the governing full-text file found no entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup.

VCEP rule
Not applicable since disease-causing variants are heterozygous.
Evidence considered
  • ClinGen Brain Malformations VCEP PM3 specification: PM3 is not applicable because disease-causing variants are heterozygous.
  • The case bundle provides no recessive inheritance, affected-proband phase, parental/offspring phase, or pathogenic variant-in-trans evidence for this variant.
  • The governing full-text file was searched for c.2107_2121dup, p.Asn703_Glu707dup, and p.N703_E707dup; no variant-specific entry was found.
Still missing
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
PM4 VCEPNot applicable: the VCEP does not use PM4 for these genes, despite this variant being a five-amino-acid in-frame duplication. Details ▾Hide ▴
Reasoning

PM4 is not applicable under the Brain Malformations VCEP specification. The variant is an in-frame duplication, NM_006218.4:c.2107_2121dup, predicted as NP_006209.2:p.(Asn703_Glu707dup), but the VCEP states that PM4 will not be used for these genes because reported in-frame indels are exceptionally rare and most insertion/deletions are associated with a loss-of-function mechanism, even though an in-frame indel could result in gain of function.

VCEP rule
Although there have been reported in-frame deletion/insertions in these genes which cause the overgrowth phenotype, they are exceptionally rare. Most insertion/deletions are associated with a LoF disease mechanism and so this point will still not be used even though we recognize that it is possible that a variant is an in-frame indel that results in a GoF mechanism.
Evidence considered
  • ClinGen Brain Malformations VCEP PM4 specification: PM4 is not applicable for these genes and will not be used for reported in-frame insertion/deletion variants.
  • Variant consequence facts: NM_006218.4:c.2107_2121dup is an in-frame duplication predicted as NP_006209.2:p.(Asn703_Glu707dup), affecting five amino acids in exon 14.
Sources
cspec ↗pvs1_variant_assessment
PM5 N/ANot applicable: PM5 requires a missense variant, and this is an in-frame indel. Details ▾Hide ▴
Reasoning

PM5 (Richards et al. 2015, PMID:25741868) requires a novel missense change at an amino acid residue where a different missense change has previously been determined to be pathogenic. NM_006218.4:c.2107_2121dup in PIK3CA is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_006209.2:p.(Asn703_Glu707dup). As a result, no missense change exists at this residue to compare against a different pathogenic missense change at the same position, so PM5's structural prerequisite is not met by this variant class. The ClinGen Brain Malformations Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1 applies PM5 as originally described in ACMG/AMP 2015, so the original definition governs. This determination was made deterministically from the variant's consequence class, prior to LLM adjudication.

Rule
deterministic_prefilter: requires_missense
Evidence considered
  • Deterministic consequence classification: in_frame_indel_unknown (prefetch.json normalized protein consequence)
  • VCEP criterion policy: vcep_unchanged
Sources
generic_acmg_combination_rulescspec ↗
PM6 VCEPNot applicable: the VCEP explicitly assigns confirmed de novo evidence without parental confirmation to PS2 rather than PM6. Details ▾Hide ▴
Reasoning

The VCEP marks PM6 as not applicable and states that confirmed de novo evidence without confirmed paternity and maternity is addressed by PS2.

VCEP rule
Confirmed de novo without confirmation of paternity and maternity. ... Addressed by PS2
Evidence considered
  • ClinGen Brain Malformations VCEP specification v1.1, PM6 row: confirmed de novo without confirmation of paternity and maternity; addressed by PS2; N/A.
Still missing
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
PP1 VCEPNot applicable: the VCEP excludes PP1 because the relevant disease-causing variants are germline mosaic, de novo, or mosaic. Details ▾Hide ▴
Reasoning

The VCEP explicitly excludes PP1 because disease-causing variants in this framework are germline mosaic, de novo, or mosaic variants.

VCEP rule
Co-segregation with disease in multiple affected family members ... Not applicable since disease-causing variants are germline mosaic, de novo or mosaic.
Evidence considered
  • ClinGen Brain Malformations VCEP specification v1.1, PP1 row: co-segregation with disease in multiple affected family members; not applicable since disease-causing variants are germline mosaic, de novo or mosaic; N/A.
Still missing
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
PP2 N/ANot applicable: the VCEP PP2 rule is for missense variants with a constraint z-score >3.09, whereas this variant is an in-frame duplication. Details ▾Hide ▴
Reasoning

The VCEP's PP2 rule is explicitly based on missense constraint and applies to PIK3CA when the missense-constraint z-score exceeds 3.09. This variant is an in-frame duplication, p.Asn703_Glu707dup, not a missense variant, so the VCEP's missense PP2 rule does not apply; no substitute constraint threshold or generic rule was used. The VCEP file search found no exact entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.

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. ... Missense constraint computed in ExAC/gnomAD was utilized. Award PP2 if the z-score > 3.09. (applicable to MTOR, PIK3CA and AKT3 but not PIK3R2)
Evidence considered
  • ClinGen Brain Malformations VCEP specification v1.1, PP2 rule: missense constraint computed in ExAC/gnomAD is used, with PP2 awarded when the z-score is >3.09 for PIK3CA.
  • Case normalization identifies NM_006218.4:c.2107_2121dup as NP_006209.2:p.(Asn703_Glu707dup), an in-frame duplication rather than a missense substitution.
  • The VCEP search returned no exact match for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup in the governing full-text file.
Still missing
  • No exact entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt; PP2 is inapplicable by variant type.
Sources
vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
PP3 VCEPNot applicable: the VCEP explicitly excludes PP3 for these gain-of-function variants. Details ▾Hide ▴
Reasoning

The governing Brain Malformations VCEP specification explicitly makes PP3 not applicable because these genes' disease mechanism is gain of function and traditional pathogenicity prediction algorithms focus on loss-of-function mechanisms. The variant is an exonic in-frame duplication, NM_006218.4:c.2107_2121dup, predicted as p.(Asn703_Glu707dup); therefore no computational predictor score is evaluated for PP3 and no prediction is double-counted elsewhere. No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.

VCEP rule
Brain Malformation Recommendation: This criterion is not applicable since these variants are GOF, and traditional mutation pathogenicity prediction algorithms focus on LOF mechanisms. Use of this criterion can be revisited if there emerges additional published experience with predictive algorithms specifically designed to detect gain of function mutations.
Evidence considered
  • ClinGen Brain Malformations VCEP specification, PP3 Brain Malformation Recommendation: PP3 is not applicable for these GOF variants because traditional mutation pathogenicity prediction algorithms focus on LOF mechanisms.
  • Case normalization identifies NM_006218.4:c.2107_2121dup as an exonic in-frame duplication with predicted protein consequence NP_006209.2:p.(Asn703_Glu707dup).
Still missing
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt; this does not alter the explicit PP3 applicability decision.
Sources
vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
PP4 VCEPNot applicable: the VCEP explicitly accounts for phenotype specificity under PS4 rather than PP4. Details ▾Hide ▴
Reasoning

The Brain Malformations VCEP explicitly makes PP4 not applicable because phenotype specificity is accounted for under PS4.

VCEP rule
This criterion is accounted for under PS4.
Evidence considered
  • ClinGen Brain Malformations VCEP PP4 entry: the criterion is accounted for under PS4.
Sources
cspec ↗
PP5 VCEPNot applicable: the VCEP prohibits use of PP5 under the ClinGen Sequence Variant Interpretation recommendation. Details ▾Hide ▴
Reasoning

The Brain Malformations VCEP explicitly states that PP5 is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.

VCEP rule
This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
Evidence considered
  • ClinGen Brain Malformations VCEP PP5 entry states that this criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
Sources
cspec ↗
BS4 VCEPNot applicable: the VCEP excludes BS4 for de novo, germline mosaic, or post-zygotic mutations in this disease framework. Details ▾Hide ▴
Reasoning

The VCEP explicitly marks BS4 as not applicable because these are de novo, germline mosaic, or post-zygotic mutations.

VCEP rule
Lack of segregation in affected members of a family ... Not applicable as these are de novo, germline mosaic or post-zygotic mutations.
Evidence considered
  • ClinGen Brain Malformations VCEP specification v1.1, BS4 row: lack of segregation in affected members of a family; not applicable as these are de novo, germline mosaic or post-zygotic mutations.
Still missing
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.
Sources
cspec ↗vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
BP1 VCEPNot applicable: the VCEP excludes BP1 for this gene. Details ▾Hide ▴
Reasoning

The ClinGen Brain Malformations Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines Version 1.1 marks BP1 as not applicable. The VCEP states: "Not applicable as LOF is not the disease mechanism." NM_006218.4:c.2107_2121dup in PIK3CA is an in-frame insertion/deletion of undetermined repeat-region status predicted to produce NP_006209.2:p.(Asn703_Glu707dup). This determination was made deterministically from the VCEP criteria specification, prior to LLM adjudication.

VCEP rule
deterministic_prefilter: vcep_not_applicable
Evidence considered
  • Deterministic consequence classification: in_frame_indel_unknown (prefetch.json normalized protein consequence)
  • VCEP criterion policy: vcep_not_applicable
Sources
cspec ↗
BP3 VCEPNot applicable: the VCEP states these genes lack exon repetitive regions without known function, the required BP3 context. Details ▾Hide ▴
Reasoning

BP3 is not applicable under the Brain Malformations VCEP specification. The VCEP explicitly states that the exon regions of the specified genes do not have repetitive regions without a known function; therefore, the in-frame duplication at NM_006218.4:c.2107_2121dup cannot receive BP3 under this framework.

VCEP rule
This is not applicable for the genes specified since the exon regions do not have repetitive regions without a known function.
Evidence considered
  • ClinGen Brain Malformations VCEP BP3 specification: BP3 is not applicable because the exon regions of the specified genes do not have repetitive regions without a known function.
  • Variant consequence facts: NM_006218.4:c.2107_2121dup is an in-frame duplication in exon 14, predicted as NP_006209.2:p.(Asn703_Glu707dup).
Sources
cspec ↗pvs1_variant_assessment
BP4 N/ANot applicable: BP4 is limited to synonymous, noncanonical intronic, or UTR variants, whereas this is an exonic in-frame duplication. Details ▾Hide ▴
Reasoning

The governing VCEP limits BP4 to synonymous variants, intronic positions outside canonical splice sites, and non-coding UTR variants, with two of three named splicing tools predicting no splicing change. This variant is an exonic in-frame duplication, NM_006218.4:c.2107_2121dup, predicted as p.(Asn703_Glu707dup), so BP4 is outside its stated scope regardless of the available SpliceAI max delta score of 0.012; that score is not evaluated for BP4. No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.

VCEP rule
Brain Malformation Recommendation: Not applicable for any variant type except for For synonymous, intronic positions (except canonical splice sites) and non-coding variants in the UTRs,. This criterion can be applied when two of three splicing prediction tools predict no splicing change. The splicing prediction tools used are: varSEAK, spliceAI and MaxEntScan.
Evidence considered
  • ClinGen Brain Malformations VCEP specification, BP4 Brain Malformation Recommendation: BP4 is not applicable except for synonymous, intronic positions outside canonical splice sites, and non-coding UTR variants; when applicable, two of three tools must predict no splicing change, using varSEAK, spliceAI, and MaxEntScan.
  • Case normalization identifies NM_006218.4:c.2107_2121dup as an exonic in-frame duplication with predicted protein consequence NP_006209.2:p.(Asn703_Glu707dup). The available SpliceAI max delta score is 0.012, but it is outside BP4's stated variant scope and is not used.
Still missing
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt; this does not alter the explicit BP4 variant-scope decision.
Sources
vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
BP6 VCEPNot applicable: the VCEP explicitly excludes BP6 from use for this framework. Details ▾Hide ▴
Reasoning

The Brain Malformations VCEP explicitly marks BP6 as not applicable and states that it is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.

VCEP rule
This criterion is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
Evidence considered
  • ClinGen Brain Malformations VCEP BP6 entry: the criterion is not applicable and is not for use as recommended by the ClinGen Sequence Variant Interpretation VCEP Review Committee.
Sources
cspec ↗
BP7 N/ANot applicable: BP7 is restricted to synonymous, noncanonical intronic, or UTR variants, not this exonic in-frame duplication. Details ▾Hide ▴
Reasoning

The governing VCEP limits BP7 to synonymous variants, intronic positions outside canonical splice sites, and non-coding UTR variants whose nucleotide is non-conserved, defined by absence in all vertebrae or a PhyloP score below 0.1. This variant is an exonic in-frame duplication, NM_006218.4:c.2107_2121dup, predicted as p.(Asn703_Glu707dup), so BP7 is outside its stated scope and no conservation or splice predictor value is needed. No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.

VCEP rule
Brain Malformation Recommendation: For synonymous, intronic positions (except canonical splice sites) and non-coding variants in the UTRs, if the nucleotide is non-conserved award this point. Not conserved is defined as the same nucleotide NOT present in all vertebrae or PhyloP score <0.1.
Evidence considered
  • ClinGen Brain Malformations VCEP specification, BP7 Brain Malformation Recommendation: BP7 applies to synonymous, intronic positions outside canonical splice sites, and non-coding UTR variants when the nucleotide is non-conserved; non-conservation is defined as the same nucleotide not being present in all vertebrae or PhyloP below 0.1.
  • Case normalization identifies NM_006218.4:c.2107_2121dup as an exonic in-frame duplication with predicted protein consequence NP_006209.2:p.(Asn703_Glu707dup).
Still missing
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt; this does not alter the explicit BP7 variant-scope decision.
Sources
vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗

Identifiers

Gene
PIK3CA
Transcript
NM_006218.4
Coding (HGVS c.)
NM_006218.4:c.2107_2121dup
Protein (HGVS p.)
NP_006209.2:p.(Asn703_Glu707dup)
GRCh38
chr3:179221075 T>TGAATAGGCAAGTCGA
GRCh37
chr3:178938863 T>TGAATAGGCAAGTCGA
Location and type
Exon 14 · in frame indel unknown

Gene diagram

Every interpreted variant in PIK3CA, mapped onto the exon structure of NM_006218.4. Select a row to find it on the plot.

PIK3CANM_006218.4
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

Not available in gnomAD-Canada v1.0.

SpliceAI and Pangolin

SpliceAI acceptor lossat -89 bp
0.009
SpliceAI acceptor gainat +65 bp
0.000
SpliceAI donor lossat +82 bp
0.006
SpliceAI donor gainat +0 bp
0.012
Pangolin splice lossmagnitude shown
-0.105
Pangolin splice gain
0.011

Other predictors

REVEL
Not available
BayesDel
Not available

How the predictions were used

PP3 VCEPNot applicable: the VCEP explicitly excludes PP3 for these gain-of-function variants. Details ▾Hide ▴
Reasoning

The governing Brain Malformations VCEP specification explicitly makes PP3 not applicable because these genes' disease mechanism is gain of function and traditional pathogenicity prediction algorithms focus on loss-of-function mechanisms. The variant is an exonic in-frame duplication, NM_006218.4:c.2107_2121dup, predicted as p.(Asn703_Glu707dup); therefore no computational predictor score is evaluated for PP3 and no prediction is double-counted elsewhere. No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.

VCEP rule
Brain Malformation Recommendation: This criterion is not applicable since these variants are GOF, and traditional mutation pathogenicity prediction algorithms focus on LOF mechanisms. Use of this criterion can be revisited if there emerges additional published experience with predictive algorithms specifically designed to detect gain of function mutations.
Evidence considered
  • ClinGen Brain Malformations VCEP specification, PP3 Brain Malformation Recommendation: PP3 is not applicable for these GOF variants because traditional mutation pathogenicity prediction algorithms focus on LOF mechanisms.
  • Case normalization identifies NM_006218.4:c.2107_2121dup as an exonic in-frame duplication with predicted protein consequence NP_006209.2:p.(Asn703_Glu707dup).
Still missing
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt; this does not alter the explicit PP3 applicability decision.
Sources
vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
BP4 N/ANot applicable: BP4 is limited to synonymous, noncanonical intronic, or UTR variants, whereas this is an exonic in-frame duplication. Details ▾Hide ▴
Reasoning

The governing VCEP limits BP4 to synonymous variants, intronic positions outside canonical splice sites, and non-coding UTR variants, with two of three named splicing tools predicting no splicing change. This variant is an exonic in-frame duplication, NM_006218.4:c.2107_2121dup, predicted as p.(Asn703_Glu707dup), so BP4 is outside its stated scope regardless of the available SpliceAI max delta score of 0.012; that score is not evaluated for BP4. No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.

VCEP rule
Brain Malformation Recommendation: Not applicable for any variant type except for For synonymous, intronic positions (except canonical splice sites) and non-coding variants in the UTRs,. This criterion can be applied when two of three splicing prediction tools predict no splicing change. The splicing prediction tools used are: varSEAK, spliceAI and MaxEntScan.
Evidence considered
  • ClinGen Brain Malformations VCEP specification, BP4 Brain Malformation Recommendation: BP4 is not applicable except for synonymous, intronic positions outside canonical splice sites, and non-coding UTR variants; when applicable, two of three tools must predict no splicing change, using varSEAK, spliceAI, and MaxEntScan.
  • Case normalization identifies NM_006218.4:c.2107_2121dup as an exonic in-frame duplication with predicted protein consequence NP_006209.2:p.(Asn703_Glu707dup). The available SpliceAI max delta score is 0.012, but it is outside BP4's stated variant scope and is not used.
Still missing
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt; this does not alter the explicit BP4 variant-scope decision.
Sources
vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗
BP7 N/ANot applicable: BP7 is restricted to synonymous, noncanonical intronic, or UTR variants, not this exonic in-frame duplication. Details ▾Hide ▴
Reasoning

The governing VCEP limits BP7 to synonymous variants, intronic positions outside canonical splice sites, and non-coding UTR variants whose nucleotide is non-conserved, defined by absence in all vertebrae or a PhyloP score below 0.1. This variant is an exonic in-frame duplication, NM_006218.4:c.2107_2121dup, predicted as p.(Asn703_Glu707dup), so BP7 is outside its stated scope and no conservation or splice predictor value is needed. No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt.

VCEP rule
Brain Malformation Recommendation: For synonymous, intronic positions (except canonical splice sites) and non-coding variants in the UTRs, if the nucleotide is non-conserved award this point. Not conserved is defined as the same nucleotide NOT present in all vertebrae or PhyloP score <0.1.
Evidence considered
  • ClinGen Brain Malformations VCEP specification, BP7 Brain Malformation Recommendation: BP7 applies to synonymous, intronic positions outside canonical splice sites, and non-coding UTR variants when the nucleotide is non-conserved; non-conservation is defined as the same nucleotide not being present in all vertebrae or PhyloP below 0.1.
  • Case normalization identifies NM_006218.4:c.2107_2121dup as an exonic in-frame duplication with predicted protein consequence NP_006209.2:p.(Asn703_Glu707dup).
Still missing
  • No entry for c.2107_2121dup, p.Asn703_Glu707dup, or p.N703_E707dup was found in clingen_brainmalform_acmg_specifications_v1_1.pdf.txt; this does not alter the explicit BP7 variant-scope decision.
Sources
vcep_clingen_brainmalform_acmg_specifications_v1_1 ↗

Statement

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).

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

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 0.012 Open source ↗
COSMIC Captured COSMIC source record Open source ↗
Cancer hotspots Captured Cancer Hotspots source record Open source ↗
OncoKB Captured OncoKB 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

Not available in gnomAD-Canada v1.0.

ClinVar

This variant is absent from ClinVar.

In silico

SpliceAI predicts no significant splice impact for this variant (max delta score = 0.01).

Functional

OncoKB did not identify variant-specific reviewed functional evidence for this variant; gene-level curated context is available for reviewer follow-up. PIK3CA, the catalytic subunit of PI3-kinase, is frequently mutated in a diverse range of cancers including breast, endometrial and cervical cancers.

Somatic

This variant does not lie in a statistically significant hotspot. This variant has not previously been reported in somatic cancers (COSMIC).

Cancer Hotspots

This variant does not lie in a statistically significant hotspot.