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_000051.4(ATM):c.6530A>C (p.Gln2177Pro)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA16613415

407515 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: e408f0ac-19eb-46b0-b9ea-3d3838b4c115

Approved on: 2024-01-25

Published on: 2024-02-14

HGVS expressions

NM_000051.4:c.6530A>C

NM_000051.4(ATM):c.6530A>C (p.Gln2177Pro)

NC_000011.10:g.108321378A>C

CM000673.2:g.108321378A>C

NC_000011.9:g.108192105A>C

CM000673.1:g.108192105A>C

NC_000011.8:g.107697315A>C

NG_009830.1:g.103547A>C

NG_054724.1:g.153455T>G

ENST00000452508.7:c.6530A>C

ENST00000713593.1:c.*6001A>C

ENST00000278616.9:c.6530A>C

ENST00000525056.2:n.949A>C

ENST00000682286.1:n.1287A>C

ENST00000682302.1:n.948A>C

ENST00000683174.1:n.8014A>C

ENST00000683524.1:n.1754A>C

ENST00000684152.1:n.2244A>C

ENST00000527805.6:c.*1594A>C

ENST00000675595.1:c.*1665A>C

ENST00000675843.1:c.6530A>C

ENST00000278616.8:c.6530A>C

ENST00000452508.6:c.6530A>C

ENST00000524792.5:n.2745A>C

ENST00000525729.5:c.641-12307T>G

ENST00000533690.5:n.1934A>C

NM_000051.3:c.6530A>C

NM_001330368.1:c.641-12307T>G

NM_001351110.1:c.*39-12307T>G

NM_001351834.1:c.6530A>C

NM_001330368.2:c.641-12307T>G

NM_001351110.2:c.*39-12307T>G

NM_001351834.2:c.6530A>C

Uncertain Significance

PM3 PP3 PM2_Supporting

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 1.2.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The c.6530A>C variant in ATM is a missense variant predicted to cause substitution of glutamine by proline at amino acid 2177 (p.Gln2177Pro). This variant is absent from gnomAD v2.1.1. This variant has been detected in 1 individual with Ataxia-Telangiectasia (PMID: 26896183). The computational predictor, Revel (Score: 0.883) predicts a damaging effect on ATM function. In summary, this variant meets criteria to be classified as a variant of uncertain significance for autosomal dominant hereditary breast cancer and autosomal recessive Ataxia-Telangiectasia based on the ACMG/AMP criteria applied, as specified by the HBOP VCEP. (PM2_supporting, PM3, PP3)

PM3

This variant has been detected in 1 individual with ataxia-telangiectasia (PMID:26896183, PM3_Moderate).

PP3

REVEL = 0.883

PM2_Supporting

This variant is absent from gnomAD v2.1.1 and v3.1.1 (PM2_Supporting).

Curation History

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