Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Link to SEPIO compliant JSON-LD document

Variant: NM_000314.6(PTEN):c.-909T>C

CA000631

127681 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 6645334e-8bca-425f-949d-27eb2959bb70

HGVS expressions

NM_000314.6:c.-909T>C

NM_000314.6(PTEN):c.-909T>C

NC_000010.11:g.87863560T>C

CM000672.2:g.87863560T>C

NC_000010.10:g.89623317T>C

CM000672.1:g.89623317T>C

NC_000010.9:g.89613297T>C

NG_007466.2:g.5123T>C

NG_033079.1:g.4878A>G

NM_000314.5:c.-909T>C

NM_001304717.2:c.-390T>C

NM_001304718.1:c.-1614T>C

ENST00000371953.7:c.-910T>C

ENST00000610634.1:c.-1012T>C

Likely Benign

BP5 BP2

PVS1 BA1 BP7 BP4 BS1 BS3 BS4 BS2 PP3 PP2 PP1 PP4 PM2 PM6 PS1 PS3 PS4 PS2 PM5 PM4 PM1

Evidence Links 0

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

PTEN c.-909T>C (NC_000010.10:g.87863560T>C) meets criteria to be classified as likely benign for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (PMID 30311380). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). BP2: Observed in trans with a pathogenic or likely pathogenic PTEN variant. (internal laboratory contributor ClinVar Organization ID 19864) BP5: Variant found in multiple cases with alternate molecular basis for disease. (internal laboratory contributors SCV000185347.1, SCV000149485.5)

BP5

1 definite co-occurrence (APC and adenomatous polyposis), others with BrCA, phenotypes overlap with PHTS Case 1: Endometrial ca in late 30s, loss of MSH2/MSH6 on IHC. FHx: father colon in 50s, pat GF colon in 30s; pat aunt ovarian in 50s; uncle colon in 40s. Family meets ACII criteria. Co-occurrence with a pathogenic mutation in MSH2. Case 2: Colon in early 30s, loss of MLH1/PMS2 on IHC. FHx: mother colon 3x in 50s; mat aunt colon in 60s; mat cousin colon in 40s; 2 mat cousins colon in 40s; mat cousin breast in 40s; pat aunt breast in 50s. Family meets ACI criteria. Co-occurrence with a pathogenic mutation in MLH1. Case 3: Proband dx with Gorlin syndrome. FHx: father Gorlin syndrome, sister Gorlin syndrome. Co-occurrence with a pathogenic mutation in PTCH1. BP5 approved by EP.

BP2

1 internal GDX case phase unk. Communication from Ambry re: CCF study patient with phase proven in trans with PATH variant. BP2 approved by EP.

PVS1