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 label mismatch: ATM vs undefined
  • 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.2284_2285del (p.Leu762fs)

CA165116

141325 (ClinVar)

Gene: ATM
Condition: ATM-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
UUID: b6231ea6-49a8-4c30-85f7-eee53908086c
Approved on: 2025-06-11
Published on: 2025-07-10

HGVS expressions

NM_000051.4:c.2284_2285del
NM_000051.4(ATM):c.2284_2285del (p.Leu762fs)
NC_000011.10:g.108257514_108257515del
CM000673.2:g.108257514_108257515del
NC_000011.9:g.108128241_108128242del
CM000673.1:g.108128241_108128242del
NC_000011.8:g.107633451_107633452del
NG_009830.1:g.39683_39684del
ENST00000452508.7:c.2284_2285del
ENST00000713593.1:c.*1755_*1756del
ENST00000278616.9:c.2284_2285del
ENST00000682516.1:n.2418_2419del
ENST00000683174.1:n.2434_2435del
ENST00000683605.1:n.1779_1780del
ENST00000684037.1:c.*1219_*1220del
ENST00000527805.6:c.2284_2285del
ENST00000675595.1:c.2119_2120del
ENST00000675843.1:c.2284_2285del
ENST00000278616.8:c.2284_2285del
ENST00000452508.6:c.2284_2285del
ENST00000527805.5:c.2284_2285del
NM_000051.3:c.2284_2285del
NM_001351834.1:c.2284_2285del
NM_001351834.2:c.2284_2285del
More

Pathogenic

Met criteria codes 3
PM3_Strong PM5_Supporting PVS1
Not Met criteria codes 2
PM2 BS1

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.2284_2285del (p.Leu762Valfs*2) variant in ATM is a frameshift 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 has been detected in at least three unrelated individuals with Ataxia-Telangiectasia (PMID: 26896183). The highest population minor allele frequency in gnomAD v4.1 is 0.00002119 in the European (non-Finnish) 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_Supporing, PM3_Strong)
Met criteria codes
PM3_Strong
This variant has been detected in at least 3 individuals with Ataxia-Telangiectasia (PMID: 26896183).
PM5_Supporting
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.
PVS1
The c.2284_2285del p.Leu762Valfs*2 variant in ATM is a frameshift 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.
Not Met criteria codes
PM2
The highest population minor allele frequency in gnomAD v4.1 is 0.00002119 in the European (non-Finnish) population (PM2_Supporting, BS1, and BA1 are not met).
BS1
No code specific comments provided, please refer to the summary above or general recommendations provided in the guideline
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.