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]

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Variant: NM_000051.4(ATM):c.1158del (p.Lys387fs)

CA166706

141887 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: 991ad4c9-4e94-4c78-8e40-cdb3f5284040

Approved on: 2024-01-25

Published on: 2024-02-14

HGVS expressions

NM_000051.4:c.1158del

NM_000051.4(ATM):c.1158del (p.Lys387fs)

NC_000011.10:g.108249025del

CM000673.2:g.108249025del

NC_000011.9:g.108119752del

CM000673.1:g.108119752del

NC_000011.8:g.107624962del

NG_009830.1:g.31194del

ENST00000452508.7:c.1158del

ENST00000713593.1:c.*629del

ENST00000278616.9:c.1158del

ENST00000682516.1:n.1292del

ENST00000682956.1:n.1292del

ENST00000683174.1:n.1308del

ENST00000683605.1:n.653del

ENST00000684037.1:c.*93del

ENST00000684061.1:n.1292del

ENST00000684179.1:n.1127del

ENST00000527805.6:c.1158del

ENST00000675595.1:c.993del

ENST00000675843.1:c.1158del

ENST00000278616.8:c.1158del

ENST00000452508.6:c.1158del

ENST00000527805.5:c.1158del

NM_000051.3:c.1158del

NM_001351834.1:c.1158del

NM_001351834.2:c.1158del

Pathogenic

PVS1 PM3 PM2_Supporting PM5_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.1158del p.Lys387Argfs*3 variant in ATM is a frameshift variant in a biologically-relevant-exon predicted to cause a premature stop codon 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 is absent from gnomAD v2.1.1. This variant has been detected in at least 3 individuals with Ataxia-Telangiectasia (PMID: 10234507, 26896183, 19147735). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant hereditary breast cancer and autosomal recessive Ataxia-Telangiectasia based on the ACMG/AMP criteria applied, as specified by the HBOP VCEP (PVS1, PM2_Supporting, PM3, PM5_supporting).

PVS1

The c.1158del (p.p.Lys387Argfs*3) variant in ATM is a frameshift variant predicted to cause a premature stop codon in biologically-relevant-exon 9/63 leading to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism (PVS1).

PM3

This variant has been detected in at least 3 individuals with Ataxia-Telangiectasia (PMID: 10234507, 26896183, 19147735 )

PM2_Supporting

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

PM5_Supporting

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.

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