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.3802del (p.Glu1267_Val1268insTer)

CA286815

127374 (ClinVar)

Gene: ATM
Condition: ATM-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: dada0935-14fc-46dd-a622-722eaf48ddea
Approved on: 2024-11-26
Published on: 2025-01-13

HGVS expressions

NM_000051.4:c.3802delG
NM_000051.4:c.3802del
NM_000051.4(ATM):c.3802del (p.Glu1267_Val1268insTer)
NC_000011.10:g.108284282del
CM000673.2:g.108284282del
NC_000011.9:g.108155009del
CM000673.1:g.108155009del
NC_000011.8:g.107660219del
NG_009830.1:g.66451del
ENST00000452508.7:c.3802del
ENST00000713593.1:c.*3273del
ENST00000278616.9:c.3802del
ENST00000682289.1:n.149del
ENST00000683174.1:n.3952del
ENST00000527805.6:c.3802del
ENST00000675595.1:c.3637del
ENST00000675843.1:c.3802del
ENST00000278616.8:c.3802del
ENST00000452508.6:c.3802del
ENST00000527805.5:c.3802del
NM_000051.3:c.3802del
NM_001351834.1:c.3802del
NM_001351834.2:c.3802del
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Pathogenic

Met criteria codes 3
PM3_Very Strong PVS1 PM5_Supporting
Not Met criteria codes 3
BA1 BS1 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.3802del (p.Val1268*) 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 several individuals with Ataxia-Telangiectasia (PMID: 9463314, 12815592, 26896183). The highest population minor allele frequency in gnomAD v2.1.1 is 0.00008473 in the Admixed American population (PM2_Supporting, BS1, and BA1 are not met). 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_Very Strong)
Met criteria codes
PM3_Very Strong
This variant was observed in several individuals with Ataxia-Telangiectasia.
PVS1
The c.3802del (p.Val1268*) 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.
PM5_Supporting
This alteration results in a termination codon upstream of the most C-terminus pathogenic alteration (p.Arg3047*)
Not Met criteria codes
BA1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.00008473 in the Admixed American population (PM2_Supporting, BS1, and BA1 are not met).
BS1
The highest population minor allele frequency in gnomAD v2.1.1 is 0.00008473 in the Admixed American population (PM2_Supporting, BS1, and BA1 are not met).
PM2
The highest population minor allele frequency in gnomAD v2.1.1 is 0.00008473 in the Admixed American population (PM2_Supporting, BS1, and BA1 are not met).
Curation History
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