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.2152dup (p.Cys718fs)

CA2499220586

1027442 (ClinVar)

Gene: ATM (HGNC:472)

Condition: ATM-related cancer predisposition (MONDO:0700270)

Inheritance Mode: Autosomal dominant inheritance

UUID: 60ff5886-a7dc-40d7-897a-e5d9a96667e1

Approved on: 2026-06-19

Published on: 2026-08-05

HGVS expressions

NM_000051.4(ATM):c.2152dup (p.Cys718fs)

NM_000051.4:c.2152dup

NC_000011.10:g.108256242dup

CM000673.2:g.108256242dup

NC_000011.9:g.108126969dup

CM000673.1:g.108126969dup

NC_000011.8:g.107632179dup

NG_009830.1:g.38411dup

ENST00000452508.7:c.2152dup

ENST00000713593.1:c.*1623dup

ENST00000278616.9:c.2152dup

ENST00000682516.1:n.2286dup

ENST00000683174.1:n.2302dup

ENST00000683605.1:n.1647dup

ENST00000684037.1:c.*1087dup

ENST00000684061.1:n.2286dup

ENST00000527805.6:c.2152dup

ENST00000675595.1:c.1987dup

ENST00000675843.1:c.2152dup

ENST00000278616.8:c.2152dup

ENST00000452508.6:c.2152dup

ENST00000527805.5:c.2152dup

NM_000051.3:c.2152dup

NM_001351834.1:c.2152dup

NM_001351834.2:c.2152dup

Pathogenic

PM5_Supporting PM2_Supporting PVS1

PM3

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 1.5.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The c.2152dup (p.Cys718Leufs*20) variant in ATM is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism. This alteration results in a termination codon upstream of the most C-terminus pathogenic alteration (ATM p.Arg3047*), as classified by the HBOP VCEP, and is expected to be more deleterious. This variant has been detected in at least one individual with Ataxia-Telangiectasia (PMID: 34445196). This variant is absent from gnomAD v4.1.0. In summary, this variant meets the criteria to be classified as pathogenic for autosomal dominant ATM-related cancer predisposition and autosomal recessive Ataxia-Telangiectasia based on the ACMG/AMP criteria applied, as specified by the HBOP VCEP. (PVS1, PM5_Supporting, PM2_Supporting)

PM5_Supporting

This alteration results in a termination codon upstream of the most C-terminal pathogenic alteration (ATM p.Arg3047*), as classified by the HBOP VCEP, and is expected to be more deleterious (PM5_Supporting).

PM2_Supporting

This variant is absent from gnomAD v4.1.0 (PM2_Supporting).

PVS1

The c.2152dup p.Cys718Leufs*20)(NM_000051.4) variant in ATM is a frameshift variant predicted to cause a premature stop codon leading to nonsense mediated decay (PVS1).

PM3

This variant has been detected in at least 1 individual with Ataxia-Telangiectasia (PMID: 34445196, PM3 not included for this variant to avoid double dipping)

Curation History

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