The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • Despite there being a valid 'cspec' property in the messages there's a discrepancy in message contents and CSPEC data: * Message Gene: ATM CSPEC Genes: [ 'ATM' ] * Message MONDOs: MONDO:0700270 CSPEC MONDO: [ 'MONDO:0016419', 'MONDO:0008840', 'MONDO:0018266' ]
  • No CSPEC computed assertion could be determined for this classification!


Variant: NM_000051.4(ATM):c.4318A>T (p.Lys1440Ter)

CA16613046

407482 (ClinVar)

Gene: ATM
Condition: ATM-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
UUID: fb2bfa34-3766-4354-b984-640d17b7d239
Approved on: 2024-11-26
Published on: 2025-01-13

HGVS expressions

NM_000051.4:c.4318A>T
NM_000051.4(ATM):c.4318A>T (p.Lys1440Ter)
NC_000011.10:g.108289683A>T
CM000673.2:g.108289683A>T
NC_000011.9:g.108160410A>T
CM000673.1:g.108160410A>T
NC_000011.8:g.107665620A>T
NG_009830.1:g.71852A>T
ENST00000452508.7:c.4318A>T
ENST00000713593.1:c.*3789A>T
ENST00000278616.9:c.4318A>T
ENST00000533733.6:n.1581A>T
ENST00000683174.1:n.4468A>T
ENST00000527805.6:c.4318A>T
ENST00000675595.1:c.4153A>T
ENST00000675843.1:c.4318A>T
ENST00000278616.8:c.4318A>T
ENST00000452508.6:c.4318A>T
ENST00000524792.5:n.533A>T
ENST00000531525.2:c.325A>T
ENST00000533733.5:n.747A>T
NM_000051.3:c.4318A>T
NM_001351834.1:c.4318A>T
NM_001351834.2:c.4318A>T
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Pathogenic

Met criteria codes 4
PM5_Supporting PM3 PVS1 PM2_Supporting

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 1.3.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hereditary Breast, Ovarian and Pancreatic Cancer VCEP
The c.4318A>T (p.Lys1440*) variant in ATM gene is a nonsense 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: 26896183). This variant is absent from gnomAD v2.1.1. In summary, this variant meets 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, PM3, PM2_Supporting)
Met criteria codes
PM5_Supporting
The c.4318A>T (p.Lys1440Ter) variant 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 deleterious(PM5_Supporting).
PM3
The c.4318A>T (p.Lys1440Ter) variant has been detected in at least one individual with Ataxia-Telangiectasia (2 points: PMID: 26896183)
PVS1
The c.4318A>T (p. Lys1440Ter) variant in ATM gene is a nonsense variant observed to cause premature truncation of the protein in exon 28/63 and is predicted to lead to nonsense mediated decay in a gene in which loss-of-function is an established disease mechanism.
PM2_Supporting
Absent from controls (or at extremely low frequency if recessive) in GnomAD (V 2.1.1)
Curation History
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