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_000314.8(PTEN):c.140G>A (p.Arg47Lys)

CA16042720

373446 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 851f4f7b-68ae-4d5e-9af3-a927611602ee

HGVS expressions

NM_000314.8:c.140G>A

NM_000314.8(PTEN):c.140G>A (p.Arg47Lys)

NC_000010.11:g.87894085G>A

CM000672.2:g.87894085G>A

NC_000010.10:g.89653842G>A

CM000672.1:g.89653842G>A

NC_000010.9:g.89643822G>A

NG_007466.2:g.35647G>A

ENST00000686459.1:c.140G>A

ENST00000688158.1:c.*275+13647G>A

ENST00000688308.1:c.140G>A

ENST00000688922.1:c.9G>A

ENST00000693560.1:c.659G>A

ENST00000371953.8:c.140G>A

ENST00000371953.7:c.140G>A

ENST00000462694.1:n.142G>A

ENST00000610634.1:c.38G>A

NM_000314.5:c.140G>A

NM_000314.6:c.140G>A

NM_001304717.2:c.659G>A

NM_001304718.1:c.-566G>A

NM_000314.7:c.140G>A

NM_001304717.5:c.659G>A

NM_001304718.2:c.-566G>A

Likely Pathogenic

PM6_Strong PM2_Supporting PS3_Moderate PP3 PP2

BA1 BS3 BS1 BP4 BP1 PP4 PM1

Evidence Links 0

Expert Panel

PTEN VCEP

Criteria Specification Information

Criteria Specification: ClinGen PTEN Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for PTEN Version 3.0.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

PTEN VCEP

NM_000314.8(PTEN):c.140G>A (p.Arg47Lys) meets criteria to be classified as Likely Pathogenic for PTEN Hamartoma Tumor syndrome in an autosomal dominant manner using modified ACMG criteria (ACMG Classification Rules Specified for PTEN Variant Curation version 3.0.0). Please see a summary of the rules and criteria codes in the “PTEN ACMG Specifications Summary” document (assertion method column). PM6_S: One proband with presumed de novo occurrence (maternity/paternity not confirmed) for a patient with highly specific phenotype (internal laboratory contributor). PS3_M: Functional studies showing a damaging effect on protein function. Phosphatase activity ≤ -1.11 per Mighell et al. 2018 (PMID: 29706350). This variant: score of -1.357001423. PP2: PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease. PP3: REVEL score > 0.7 (score of this variant =0.903) PM2_P: Absent in the gnomAD cohort. (PMID 27535533).

PM6_Strong

One proband with presumed de novo occurrence (maternity/paternity not confirmed) for a patient with highly specific phenotype (internal laboratory contributor).

PM2_Supporting

Absent in gnomAD

PS3_Moderate

Functional studies showing a damaging effect on protein function. Phosphatase activity ≤ -1.11 per Mighell et al. 2018 (PMID: 29706350). This variant: score of -1.357001423.

PP3

REVEL Score is 0.903 (>0.75)

PP2

PTEN is defined by the PTEN Expert Panel as a gene that has a low rate of benign missense variation and where missense variants are a common mechanism of disease.

BA1