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.2T>C (p.Met1Thr)

Curation Version - 2.0
Curation History
JSON LD for Version 2.0

CA197209

187275 (ClinVar)

Gene: ATM

Condition: ATM-related cancer predisposition

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: af70c135-df1b-4c1e-becb-96e5c6882dd5

Approved on: 2022-03-16

Published on: 2025-09-15

HGVS expressions

NM_000051.4:c.2T>C

NM_000051.4(ATM):c.2T>C (p.Met1Thr)

NC_000011.10:g.108227626T>C

CM000673.2:g.108227626T>C

NC_000011.9:g.108098353T>C

CM000673.1:g.108098353T>C

NC_000011.8:g.107603563T>C

NG_009830.1:g.9795T>C

ENST00000452508.7:c.2T>C

ENST00000683914.2:c.2T>C

ENST00000713593.1:c.2T>C

ENST00000278616.9:c.2T>C

ENST00000682147.1:n.136T>C

ENST00000682430.1:n.101T>C

ENST00000682465.1:c.2T>C

ENST00000682516.1:n.136T>C

ENST00000682956.1:n.136T>C

ENST00000683150.1:c.2T>C

ENST00000683174.1:n.152T>C

ENST00000683468.1:c.2T>C

ENST00000683488.1:n.4583T>C

ENST00000683914.1:c.2T>C

ENST00000684029.1:c.2T>C

ENST00000684037.1:c.2T>C

ENST00000684061.1:n.136T>C

ENST00000684179.1:n.136T>C

ENST00000527805.6:c.2T>C

ENST00000638443.1:c.2T>C

ENST00000639240.1:c.2T>C

ENST00000639953.1:c.2T>C

ENST00000640388.1:c.2T>C

ENST00000675595.1:c.2T>C

ENST00000675843.1:c.2T>C

ENST00000278616.8:c.2T>C

ENST00000452508.6:c.2T>C

ENST00000526567.5:c.2T>C

ENST00000527805.5:c.2T>C

ENST00000527891.5:c.2T>C

ENST00000530958.5:c.2T>C

ENST00000532931.5:c.2T>C

ENST00000601453.2:c.2T>C

NM_000051.3:c.2T>C

NM_001351834.1:c.2T>C

NM_001351835.1:c.2T>C

NM_001351836.1:c.2T>C

NM_001351834.2:c.2T>C

NM_001351835.2:c.2T>C

NM_001351836.2:c.2T>C

Pathogenic

PM3_Very Strong PVS1 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 1.1

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The ATM c.2T>C (p.M1?) variant impacts the initiation codon and is not expected to produce a fully functional protein (PVS1). This variant has been observed in a compound heterozygous state in multiple individuals with Ataxia-Telangiectasia (PMIDs: 22146522, 3054930, 12552559, PM3_VeryStrong). This alteration has an allele frequency below 0.001% in the European (non-Finnish) subpopulation in GnomAD (PM2_Supporting). In summary, this variant meets criteria to be classified as pathogenic. ACMG/AMP criteria applied, as specified by the HBOP Variant Curation Expert Panel.

PM3_Very Strong

This variant has been observed in a compound heterozygous state (presumed) in multiple individuals with biallelic disease (PM3_VeryStrong, PMIDs: 30549301, 12552559, 22146522).

PVS1

The c.2T>C variant impacts the initiation codon which is known to disrupt protein function (PVS1)

PM2_Supporting

GnomAD AF 0.0009% (EUR) is less than ATM PM2 threshold of 0.001%

Curation History

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