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.5692C>T (p.Arg1898Ter)

CA6265757

482526 (ClinVar)

Gene: ATM
Condition: ATM-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 34d24ddc-0aa5-4b5e-8bd3-2718b7b7ed8c
Approved on: 2024-11-26
Published on: 2025-01-13

HGVS expressions

NM_000051.4:c.5692C>T
NM_000051.4(ATM):c.5692C>T (p.Arg1898Ter)
NC_000011.10:g.108307914C>T
CM000673.2:g.108307914C>T
NC_000011.9:g.108178641C>T
CM000673.1:g.108178641C>T
NC_000011.8:g.107683851C>T
NG_009830.1:g.90083C>T
NG_054724.1:g.166919G>A
ENST00000452508.7:c.5692C>T
ENST00000713593.1:c.*5163C>T
ENST00000278616.9:c.5692C>T
ENST00000525056.2:n.111C>T
ENST00000682286.1:n.449C>T
ENST00000682302.1:n.110C>T
ENST00000683174.1:n.7176C>T
ENST00000683524.1:n.916C>T
ENST00000684152.1:n.1406C>T
ENST00000527805.6:c.*756C>T
ENST00000675595.1:c.*756C>T
ENST00000675843.1:c.5692C>T
ENST00000278616.8:c.5692C>T
ENST00000452508.6:c.5692C>T
ENST00000524792.5:n.1907C>T
ENST00000529588.5:c.187-2246C>T
ENST00000533690.5:n.1096C>T
NM_000051.3:c.5692C>T
NM_001351834.1:c.5692C>T
NM_001351834.2:c.5692C>T
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Pathogenic

Met criteria codes 3
PVS1 PM5_Supporting PM3_Strong
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 1.3.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Hereditary Breast, Ovarian and Pancreatic Cancer VCEP
The c.5692 C>T (p.Arg1898*) variant in ATM 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-terminal 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 2 individuals with Ataxia-Telangiectasia (PMID: 17124347, 26896183). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00003268 in the South Asian population (PM2_Supporting, BS1, and BA1 are not met). In summary, this variant meets the 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_Strong)
Met criteria codes
PVS1
The c.5692 C>T (p.Arg1898*) (NM_000051.4) variant in ATM is a nonsense variant predicted to cause a premature stop codon in biologically-relevant-exon leading to nonsense mediated decay (PVS1).
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_Strong
This variant has been detected in 2 unrelated individuals with Ataxia-Telangiectasia (PMID: 17124347, 26896183).
Not Met criteria codes
PM2
The highest minor allele frequency in gnomAD v2.1.1 is 0.00003268 (1/30598 alleles) in South Asian population, which is higher than the ClinGen HBOP VCEP threshold (>.001%, ) for PM2_Supporting.
Curation History
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