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_000051.3(ATM):c.3137T>C (p.Leu1046Pro)

Curation Version - 1.3
Curation History
JSON LD for Version 1.3

CA195169

186558 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 3eed550b-ae19-4435-acea-e76457ec9345

Approved on: 2022-03-16

Published on: 2022-07-12

HGVS expressions

NM_000051.3:c.3137T>C

NM_000051.3(ATM):c.3137T>C (p.Leu1046Pro)

NC_000011.10:g.108272591T>C

CM000673.2:g.108272591T>C

NC_000011.9:g.108143318T>C

CM000673.1:g.108143318T>C

NC_000011.8:g.107648528T>C

NG_009830.1:g.54760T>C

ENST00000278616.9:c.3137T>C

ENST00000683174.1:n.3287T>C

ENST00000527805.6:c.3137T>C

ENST00000675595.1:c.2972T>C

ENST00000675843.1:c.3137T>C

ENST00000278616.8:c.3137T>C

ENST00000452508.6:c.3137T>C

ENST00000527805.5:c.3137T>C

NM_001351834.1:c.3137T>C

NM_001351834.2:c.3137T>C

NM_000051.4:c.3137T>C

NM_000051.4(ATM):c.3137T>C (p.Leu1046Pro)

Likely Pathogenic

PP3 PM2_Supporting PM3_Strong

Evidence Links 0

Expert Panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

Criteria Specification Information

Criteria Specification: ClinGen Hereditary Breast, Ovarian and Pancreatic Cancer Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for ATM Version 1.1

PDF

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The ATM c.3137T>C (p.Leu1046Pro) variant is absent in GnomAD v2.1.1 (PM2_Supporting). In silico protein predictors (REVEL Impact: 0.854; Align-GVGD: C65) predict that this alteration is deleterious (PP3). This variant has also been observed in a homozygous and compound heterozygous state (presumed) in multiple individuals with ataxia-telangiectasia (PMIDs: 27664052, 31429931) (PM3_Strong). In summary, this variant meets criteria to be classified as likely pathogenic based on the ACMG/AMP criteria applied as specified by the HBOP Variant Curation Expert Panel.

PP3

In silico protein predictors (REVEL Impact: 0.854; Align-GVGD: C65) predict that this alteration is deleterious (PP3).

PM2_Supporting

This variant is absent in GnomAD v2.1.1 (PM2_Supporting).

PM3_Strong

This variant has been observed in a homozygous and compound heterozygous state (presumed) in multiple individuals with Ataxia-Telangiectasia (27664052, 31429931: PM3_Strong) (4)

Curation History

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