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]

Link to SEPIO compliant JSON-LD document

Variant: NM_000051.4(ATM):c.790del (p.Tyr264fs)

CA166283

141742 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: d3ead41c-4b75-4c13-83f1-65dddcea0ee9

HGVS expressions

NM_000051.4:c.790del

NM_000051.4(ATM):c.790del (p.Tyr264fs)

NC_000011.10:g.108244915del

CM000673.2:g.108244915del

NC_000011.9:g.108115642del

CM000673.1:g.108115642del

NC_000011.8:g.107620852del

NG_009830.1:g.27084del

ENST00000452508.7:c.790del

ENST00000713593.1:c.*261del

ENST00000278616.9:c.790del

ENST00000682430.1:n.889del

ENST00000682516.1:n.924del

ENST00000682956.1:n.924del

ENST00000683100.1:n.3137del

ENST00000683174.1:n.940del

ENST00000683605.1:n.285del

ENST00000684037.1:c.790del

ENST00000684061.1:n.924del

ENST00000684179.1:n.759del

ENST00000527805.6:c.790del

ENST00000675595.1:c.625del

ENST00000675843.1:c.790del

ENST00000278616.8:c.790del

ENST00000452508.6:c.790del

ENST00000527805.5:c.790del

NM_000051.3:c.790del

NM_001351834.1:c.790del

NM_001351834.2:c.790del

Pathogenic

PVS1 PM3_Strong PM5_Supporting

PM2

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.790delT (p.Y264Ifs*12) variant in ATM is a frameshift variant predicted to cause a premature stop codon in a 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-terminal pathogenic alteration (ATM p.Arg3047*), as classified by the HBOP VCEP, and is expected to be more deleterious. This variant has a minor allele frequency in gnomAD v2.1.1 of 0.00001763 (2/113450 alleles) in European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met). This variant has been detected in at least 4 individuals with Ataxia-Telangiectasia (PMID: 12815592, 9887333, 26896183, 22213089). In summary, this variant meets the criteria to be classified as a pathogenic variant 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, PM3_strong, PM5_supporting)

PVS1

The c.790delT(p.Y264Ifs*12)(NM_000051.4) variant in ATM is a frameshift deletion variant predicted to cause a premature stop codon in biologically-relevant-exon 6 leading to nonsense mediated decay(PVS1).

PM3_Strong

This variant has been detected in 4 unrelated individuals with Ataxia Telangiectasia (PMID: 12815592, 9887333, 26896183, 22213089).

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.

PM2

This variant has a minor allele frequency in gnomAD v2.1.1 of 0.00001763 (2/113450 alleles) in European (non-Finnish) population (PM2_Supporting not met).

Approved on: 2024-01-25

Published on: 2024-02-14

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