Genetic Information
Gene & Transcript Details
| ID | Status | Details |
|---|---|---|
| NM_000314.8 | MANE Select | 8515 nt | 846–2057 |
| 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 |
Variant Details
Clinical & Population Data
Population Frequency
gnomADClinVar
Open""
COSMIC Somatic Evidence
Open
Functional Impact & Domains
Functional Domain
Computational Analysis
Pathogenicity Predictions
SpliceAISpliceAI Scores
Window: ±500bp| Effect Type | Score | Position |
|---|---|---|
| Acceptor Loss (AL) | 0.21 | -81 bp |
| Donor Loss (DL) | 0.39 | 10 bp |
| Acceptor Gain (AG) | 0.0 | 10 bp |
| Donor Gain (DG) | 0.0 | -3 bp |
VCEP Guidelines
Applied ACMG/AMP Criteria (VCEP Specific)
PVS1 (Not Applied)
According to VCEP guidelines, the rule for PVS1 is: "Very Strong: Use PTEN PVS1 decision tree." The variant is an in-frame deletion/insertion not predicted to result in a null allele. Therefore, this criterion is not applied because the variant does not meet the null variant requirement.
PS1 (Not Applied)
According to VCEP guidelines, the rule for PS1 is: "Strong: Same amino acid change as a previously established pathogenic variant regardless of nucleotide change." The variant does not result in a previously established pathogenic amino acid change. Therefore, PS1 is not applied.
PS2 (Not Applied)
According to VCEP guidelines, the rule for PS2 is: "Strong: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history." No de novo data are available. Therefore, PS2 is not applied.
PS3 (Not Applied)
According to PTEN Pre-processing, functional studies (PS3) were not available: "The PTEN D52_R55delinsG variant has not been functionally characterized." Therefore, PS3 is not applied due to lack of well-established functional evidence.
PS4 (Not Applied)
According to VCEP guidelines, the rule for PS4 is: "Strong: Prevalence in affected individuals significantly increased compared with controls or specificity score 4-15.5." No case data or specificity score are available. Therefore, PS4 is not applied.
PM1 (Not Applied)
According to VCEP guidelines, the rule for PM1 is: "Moderate: Located in a mutational hotspot or critical functional domain (residues 90-94,123-130,166-168)." The variant affects residues 52-55 outside of defined PTEN catalytic motifs. Therefore, PM1 is not applied.
PM2 (Supporting)
According to VCEP guidelines, the rule for PM2 is: "Supporting: Absent in population databases present at <0.00001 allele frequency in gnomAD." The variant is absent from gnomAD and other control databases. Therefore, PM2 is applied at Supporting strength because the variant is absent from controls.
PM3 (Not Applied)
According to standard ACMG guidelines, the rule for PM3 is: "Moderate: For recessive disorders, detected in trans with a pathogenic variant." No evidence of compound heterozygosity or trans configuration is available. Therefore, PM3 is not applied.
PM4 (Moderate)
According to VCEP guidelines, the rule for PM4 is: "Moderate: Protein length changes due to in-frame deletions/insertions in a non-repeat region." The variant causes an in-frame deletion/insertion of residues D52_R55delinsG, altering protein length. Therefore, PM4 is applied at Moderate strength.
PM5 (Not Applied)
According to VCEP guidelines, the rule for PM5 is: "Moderate: Missense change at a residue where a different missense change is pathogenic." This variant is an in-frame indel, not a missense. Therefore, PM5 is not applied.
PM6 (Not Applied)
According to VCEP guidelines, the rule for PM6 is: "Moderate: Assumed de novo without confirmation." No de novo assumptions are documented. Therefore, PM6 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 (3-4 meioses)." No segregation data are available. Therefore, PP1 is not applied.
PP2 (Not Applied)
According to standard ACMG guidelines, the rule for PP2 is: "Supporting: Missense variant in a gene with low rate of benign missense variation where missense is common mechanism." This is an in-frame indel, not a missense. Therefore, PP2 is not applied.
PP3 (Not Applied)
According to VCEP guidelines, the rule for PP3 is: "Supporting: Multiple lines of computational evidence support deleterious effect (REVEL>0.7 or splicing concordance)." Computational predictions are inconclusive (SpliceAI max 0.39, no REVEL). Therefore, PP3 is not applied.
PP4 (Not Applied)
According to standard ACMG guidelines, the rule for PP4 is: "Supporting: Patient’s phenotype is highly specific for gene." No phenotype or case-specific data are provided. Therefore, PP4 is not applied.
PP5 (Not Applied)
According to standard ACMG guidelines, the rule for PP5 is: "Supporting: Reputable source reports variant as pathogenic." The variant is not found in ClinVar or other expert databases. Therefore, PP5 is not applied.
BA1 (Not Applied)
According to VCEP guidelines, the rule for BA1 is: "Stand Alone: gnomAD allele frequency >0.00056." The variant is absent from population databases. Therefore, BA1 is not applied.
BS1 (Not Applied)
According to VCEP guidelines, the rule for BS1 is: "Strong: gnomAD allele frequency 0.000043–0.00056." The variant is absent from population databases. Therefore, BS1 is not applied.
BS2 (Not Applied)
According to VCEP guidelines, the rule for BS2 is: "Strong: Observed homozygous in a healthy individual." No homozygous observations are reported. Therefore, BS2 is not applied.
BS3 (Not Applied)
According to VCEP guidelines, the rule for BS3 is: "Strong: Well-established functional studies show no damaging effect." No functional studies are available. Therefore, BS3 is not applied.
BS4 (Not Applied)
According to VCEP guidelines, the rule for BS4 is: "Strong: Lack of segregation in affected members of two or more families." No segregation data are available. Therefore, BS4 is not applied.
BP1 (Not Applied)
According to standard ACMG guidelines, the rule for BP1 is: "Supporting: Missense in a gene where only truncating variants cause disease." This is an in-frame indel. Therefore, BP1 is not applied.
BP2 (Not Applied)
According to VCEP guidelines, the rule for BP2 is: "Supporting: Observed in trans with a pathogenic variant." No such observations are available. Therefore, BP2 is not applied.
BP3 (Not Applied)
According to VCEP guidelines, the rule for BP3 is: "Supporting: In-frame indels in repetitive region." The variant affects a non-repeat region. Therefore, BP3 is not applied.
BP4 (Not Applied)
According to VCEP guidelines, the rule for BP4 is: "Supporting: Multiple lines of computational evidence suggest no impact (REVEL<0.5 or splicing concordance)." Computational evidence is inconclusive. Therefore, BP4 is not applied.
BP5 (Not Applied)
According to VCEP guidelines, the rule for BP5 is: "Supporting: Variant found in a case with an alternate molecular basis." No alternate molecular basis is reported. Therefore, BP5 is not applied.
BP6 (Not Applied)
According to standard ACMG guidelines, the rule for BP6 is: "Supporting: Reputable source reports as benign." The variant is not found in expert-curated benign listings. Therefore, BP6 is not applied.
BP7 (Not Applied)
According to VCEP guidelines, the rule for BP7 is: "Supporting: Synonymous or intronic variant predicted no splicing impact." This is a coding in-frame indel. Therefore, BP7 is not applied.