Evidence Repository
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.2413C>T (p.Arg805Ter)

CA338870

216021 (ClinVar)

Gene: ATM
Condition: hereditary breast cancer
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 0dc372aa-be88-4449-b455-5343fabc61bc
Approved on: 2024-01-25
Published on: 2024-02-14

HGVS expressions

NM_000051.4:c.2413C>T
NM_000051.4(ATM):c.2413C>T (p.Arg805Ter)
NC_000011.10:g.108259022C>T
CM000673.2:g.108259022C>T
NC_000011.9:g.108129749C>T
CM000673.1:g.108129749C>T
NC_000011.8:g.107634959C>T
NG_009830.1:g.41191C>T
ENST00000452508.7:c.2413C>T
ENST00000713593.1:c.*1884C>T
ENST00000278616.9:c.2413C>T
ENST00000682516.1:n.2547C>T
ENST00000683174.1:n.2563C>T
ENST00000683605.1:n.1908C>T
ENST00000684037.1:c.*1348C>T
ENST00000527805.6:c.2413C>T
ENST00000675595.1:c.2248C>T
ENST00000675843.1:c.2413C>T
ENST00000278616.8:c.2413C>T
ENST00000452508.6:c.2413C>T
ENST00000527805.5:c.2413C>T
NM_000051.3:c.2413C>T
NM_001351834.1:c.2413C>T
NM_001351834.2:c.2413C>T
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Pathogenic

Met criteria codes 3
PM5_Supporting PM3_Very Strong PVS1
Not Met criteria codes 1
PM2

Evidence Links 0

Expert Panel

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.2413C>T (p.Arg805Ter) variant in ATM is a nonsense 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. The highest minor allele frequency in gnomAD v2.1.1 is 0.0003263 (6/18388) in the East Asian population (PM2_Supporting, BS1, and BA1 are not met). This variant has been detected in at least 6 individuals with Ataxia-Telangiectasia (PMID: 26896183, 12815592, 15843990, 16941484, 23807571). 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, PM3_very strong, PM5_Supporting)
Met criteria codes
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).
PM3_Very Strong
This variant has been detected in 6 unrelated individuals with Ataxia Telangiectasia (PM3_very strong; PMID: 26896183, 12815592, 15843990, 16941484, 23807571).
PVS1
This variant is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon 15 leading to nonsense mediated decay (PVS1).
Not Met criteria codes
PM2
This variant has a minor allele frequency in gnomAD v2.1.1 of 0.0003263 (6/18388) in the East Asian population (PM2_Supporting not met).
Curation History
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