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]

Variant: NM_000314.6(PTEN):c.492+2T>G

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA000475

7821 (ClinVar)

Gene: PTEN

Condition: PTEN hamartoma tumor syndrome

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 97d2ac8e-89b9-466c-a53a-4e15d173a70a

Approved on: 2023-06-14

Published on: 2023-10-19

HGVS expressions

NM_000314.6:c.492+2T>G

NM_000314.6(PTEN):c.492+2T>G

NC_000010.11:g.87933253T>G

CM000672.2:g.87933253T>G

NC_000010.10:g.89693010T>G

CM000672.1:g.89693010T>G

NC_000010.9:g.89682990T>G

NG_007466.2:g.74815T>G

ENST00000686459.1:c.492+2T>G

ENST00000688158.1:c.*603+2T>G

ENST00000688308.1:c.492+2T>G

ENST00000688922.1:c.413+2T>G

ENST00000693560.1:c.1011+2T>G

ENST00000371953.8:c.492+2T>G

ENST00000371953.7:c.492+2T>G

ENST00000498703.1:n.320T>G

ENST00000610634.1:c.390+2T>G

NM_000314.5:c.492+2T>G

NM_001304717.2:c.1011+2T>G

NM_001304718.1:c.-259+2T>G

NM_000314.7:c.492+2T>G

NM_001304717.5:c.1011+2T>G

NM_001304718.2:c.-259+2T>G

NM_000314.8:c.492+2T>G

NM_000314.8(PTEN):c.492+2T>G

Pathogenic

PM2_Supporting PS4_Supporting PS2 PVS1

BS2 BS3 BS4 BS1 BP5 BP7 BP2 BP3 BP1 BP4 PS3 PS1 PP4 PP1 PP2 PP3 BA1 PM6 PM3 PM1 PM4 PM5

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.492+2T>G variant meets criteria to be classified as 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). PVS1: Null variant predicted to result in nonsense-mediated decay or causing truncation/frameshift at or 5’ to c.1121 (NM_000314.8). PS2: De novo (both maternity and paternity confirmed) observation in a patient with the disease and no family history. (SCV002821528.2). PM2_P: Absent in large sequenced populations OR present at extremely low (<0.00001, 0.001%) allele frequency in the gnomAD cohort. (PMID 27535533). PS4_P: Proband(s) with phenotype specificity score of 1-1.5. (SCV001499809.1)

PM2_Supporting

This variant is completely absent from gnomAD/ExAC databases (PM2_Supporting).

PS4_Supporting

This variant has been reported in one proband meeting Cleveland Clinic (CC) criteria. CC score=38=1 point (PS4_ Supporting; SCV001499809.1).

PS2

This variant has been identified as a de novo occurrence with confirmed parental relationships in 1 individual (PS2, SCV002821528.2)

PVS1

Exon skipping or use of a cryptic splice site disrupts reading frame and is predicted to undergo NMD. Disruption at or 5’ to p.D375 (c.1121).

BS2