Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_000314.7 | RefSeq Select | 8514 nt | 845–2056 |
| NM_000314.5 | Alternative | 8719 nt | 1032–2243 |
| NM_000314.4 | Alternative | 5572 nt | 1032–2243 |
| NM_000314.3 | Alternative | 3416 nt | 1032–2243 |
| NM_000314.6 | Alternative | 8718 nt | 1032–2243 |
| NM_000314.8 | MANE Select | 8515 nt | 846–2057 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
Open""
COSMIC Somatic Evidence
OpenFunctional Impact & Domains
Functional Domain
Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.09 | -29 bp |
| Donor Loss (DL) | 0.0 | 83 bp |
| Acceptor Gain (AG) | 0.01 | -227 bp |
| Donor Gain (DG) | 0.01 | -104 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PVS1 (Very Strong)
According to VCEP guidelines, the rule for PVS1 is: "Very Strong Use PTEN PVS1 decision tree." The evidence for this variant shows: NM_000314.8:c.719_720del is a frameshift leading to Y240Ffs*2, predicted to result in loss of function in a gene where LOF is a known mechanism and it is not in the last exon. Therefore, this criterion is applied at Very Strong strength because it meets the PTEN-specific PVS1 decision tree for a truncating variant outside the last exon.
PS1 (Not Applied)
According to VCEP guidelines, the rule for PS1 is: "Same amino acid change as a previously established pathogenic variant regardless of nucleotide change..." The evidence for this variant shows: it is a frameshift, not a missense change matching an established pathogenic variant. Therefore, this criterion is not applied.
PS2 (Not Applied)
According to VCEP guidelines, the rule for PS2 is: "Very Strong: Two proven OR four assumed OR one proven + two assumed de novo observations..." The evidence for this variant shows: no de novo data are available. Therefore, this criterion is not applied.
PS3 (Not Applied)
According to VCEP guidelines for PS3, the rule is: "Strong: Well-established in vitro or in vivo functional studies supportive of a damaging effect..." The evidence for this variant shows: no functional studies (e.g., phosphatase assays) are available. Therefore, this criterion is not applied.
PS4 (Not Applied)
According to VCEP guidelines, the rule for PS4 is: "Strong: Probands with specificity score 4–15.5 OR significant increase in prevalence in cases vs controls..." The evidence for this variant shows: no case-level prevalence or specificity score data are available. Therefore, this criterion is not applied.
PM1 (Not Applied)
According to VCEP guidelines, the rule for PM1 is: "Moderate: Located in a mutational hotspot and/or critical functional domain (residues 90–94, 123–130, 166–168)." The evidence for this variant shows: position 240 is outside these defined motifs. Therefore, this criterion is not applied.
PM2 (Supporting)
According to VCEP guidelines, the rule for PM2 is: "Supporting: Absent in population databases at <0.00001 allele frequency in gnomAD." The evidence for this variant shows: MAF = 0% in gnomAD and other databases. Therefore, this criterion is applied at Supporting strength because the variant is absent from controls.
PM3 (Not Applied)
According to VCEP guidelines, the rule for PM3 is: "Moderate: Detected in trans with a pathogenic variant for a recessive disorder..." The evidence for this variant shows: PTEN-related disease is autosomal dominant, and no trans data are relevant. Therefore, this criterion is not applied.
PM4 (Not Applied)
According to VCEP guidelines, the rule for PM4 is: "Moderate: Protein length changes due to in-frame deletions/insertions..." The evidence for this variant shows: it is a frameshift rather than an in-frame change. Therefore, this criterion is not applied.
PM5 (Not Applied)
According to VCEP guidelines, the rule for PM5 is: "Moderate: Missense change at a residue where a different missense variant is pathogenic..." The evidence for this variant shows: it is not a missense variant. Therefore, this criterion is not applied.
PM6 (Not Applied)
According to VCEP guidelines, the rule for PM6 is: "Very Strong/Strong/Moderate: Assumed de novo occurrences without confirmation..." The evidence for this variant shows: no de novo assumptions are available. Therefore, this criterion is not applied.
PP1 (Not Applied)
According to VCEP guidelines, the rule for PP1 is: "Supporting: Co-segregation with disease in multiple affected family members..." The evidence for this variant shows: no segregation data are available. Therefore, this criterion is not applied.
PP2 (Not Applied)
According to standard ACMG guidelines, the rule for PP2 is: "Supporting: Missense variant in a gene with low benign missense rate and where missense is common mechanism..." The evidence for this variant shows: it is a frameshift, not a missense variant. Therefore, this criterion is not applied.
PP3 (Not Applied)
According to VCEP guidelines, the rule for PP3 is: "Supporting: Computational evidence supports a deleterious effect (REVEL >0.7 or concordant splice predictions)." The evidence for this variant shows: computational tools are not relevant for a LOF frameshift and SpliceAI score is low for splicing. Therefore, this criterion is not applied.
PP4 (Not Applied)
According to standard ACMG guidelines, the rule for PP4 is: "Supporting: Patient phenotype or family history is highly specific for a disease with a single genetic etiology..." The evidence for this variant shows: no phenotype data are provided. Therefore, this criterion is not applied.
PP5 (Not Applied)
According to standard ACMG guidelines, the rule for PP5 is: "Supporting: Reputable source reports variant as pathogenic..." The evidence for this variant shows: not reported in ClinVar or similar. Therefore, this criterion is not applied.
BA1 (Not Applied)
According to VCEP guidelines, the rule for BA1 is: "Stand Alone: gnomAD frequency >0.00056." The evidence for this variant shows: frequency = 0%. Therefore, this criterion is not applied.
BS1 (Not Applied)
According to VCEP guidelines, the rule for BS1 is: "Strong: gnomAD frequency 0.000043–0.00056." The evidence for this variant shows: frequency = 0%. Therefore, this criterion is not applied.
BS2 (Not Applied)
According to VCEP guidelines, the rule for BS2 is: "Strong: Observed homozygous in healthy individual..." The evidence for this variant shows: no homozygous observations. Therefore, this criterion is not applied.
BS3 (Not Applied)
According to VCEP guidelines, the rule for BS3 is: "Strong: Well-established functional studies show no damaging effect..." The evidence for this variant shows: no such studies. Therefore, this criterion is not applied.
BS4 (Not Applied)
According to VCEP guidelines, the rule for BS4 is: "Strong: Lack of segregation in two or more families..." The evidence for this variant shows: no segregation data. Therefore, this criterion is not applied.
BP1 (Not Applied)
According to standard ACMG guidelines, the rule for BP1 is: "Supporting: Missense in a gene for which only LOF causes disease..." The evidence for this variant shows: it is LOF rather than missense. Therefore, this criterion is not applied.
BP2 (Not Applied)
According to VCEP guidelines, the rule for BP2 is: "Supporting: Observed in trans with a pathogenic variant in recessive context..." The evidence for this variant shows: no trans data. Therefore, this criterion is not applied.
BP3 (Not Applied)
According to standard ACMG guidelines, the rule for BP3 is: "Supporting: In-frame indel in a repetitive region without a known function..." The evidence for this variant shows: it is a frameshift. Therefore, this criterion is not applied.
BP4 (Not Applied)
According to VCEP guidelines, the rule for BP4 is: "Supporting: Computational evidence suggests no impact (REVEL <0.5 or concordant splice predictions)." The evidence for this variant shows: computational data are not relevant for LOF frameshift. Therefore, this criterion is not applied.
BP5 (Not Applied)
According to VCEP guidelines, the rule for BP5 is: "Supporting: Variant found with an alternate molecular basis for disease..." The evidence for this variant shows: no alternate molecular basis reported. Therefore, this criterion is not applied.
BP6 (Not Applied)
According to standard ACMG guidelines, the rule for BP6 is: "Supporting: Reputable source reports variant as benign..." The evidence for this variant shows: no such reports. Therefore, this criterion is not applied.
BP7 (Not Applied)
According to VCEP guidelines, the rule for BP7 is: "Supporting: Synonymous or intronic variant with no splicing impact..." The evidence for this variant shows: it is a frameshift. Therefore, this criterion is not applied.