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]
  • 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.1396C>T (p.Gln466Ter)

CA10579008

233553 (ClinVar)

Gene: ATM
Condition: ATM-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 88756329-6368-459a-b1e3-a90dc4a0673c
Approved on: 2024-11-26
Published on: 2025-01-13

HGVS expressions

NM_000051.4:c.1396C>T
NM_000051.4(ATM):c.1396C>T (p.Gln466Ter)
NC_000011.10:g.108250861C>T
CM000673.2:g.108250861C>T
NC_000011.9:g.108121588C>T
CM000673.1:g.108121588C>T
NC_000011.8:g.107626798C>T
NG_009830.1:g.33030C>T
ENST00000452508.7:c.1396C>T
ENST00000713593.1:c.*867C>T
ENST00000278616.9:c.1396C>T
ENST00000682516.1:n.1530C>T
ENST00000682956.1:n.1530C>T
ENST00000683174.1:n.1546C>T
ENST00000683605.1:n.891C>T
ENST00000684037.1:c.*331C>T
ENST00000684061.1:n.1530C>T
ENST00000684179.1:n.1365C>T
ENST00000527805.6:c.1396C>T
ENST00000675595.1:c.1231C>T
ENST00000675843.1:c.1396C>T
ENST00000278616.8:c.1396C>T
ENST00000452508.6:c.1396C>T
ENST00000527805.5:c.1396C>T
NM_000051.3:c.1396C>T
NM_001351834.1:c.1396C>T
NM_001351834.2:c.1396C>T
More

Pathogenic

Met criteria codes 4
PM5_Supporting PM2_Supporting PVS1 PM3_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.1396C>T (p.Gln466*) variant in ATM is a nonsense 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 was observed in at least 1 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 Variant Curation Expert Panel. (PVS1, PM5_Supporting, PM3_Supporting, PM2_Supporting)
Met criteria codes
PM5_Supporting
This alteration results in a termination codon upstream of the most C-terminus pathogenic alteration (p.Arg3047*)
PM2_Supporting
This Variant is absent from gnomAD v2.1.1
PVS1
This variant in ATM is a nonsense variant 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
PM3_Supporting
This variant was also observed in the compound heterozygous state in an individual with ataxia-telangiectasia.
Curation History
The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.
¤ Powered by BCM's Genboree.