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.8307G>A (p.Trp2769Ter)

CA334794

189104 (ClinVar)

Gene: ATM
Condition: ATM-related cancer predisposition
Inheritance Mode: Autosomal dominant inheritance
Link to MONDO
UUID: 1bc61c97-9ae1-4c72-83ab-128df71d03a8
Approved on: 2024-11-26
Published on: 2025-01-13

HGVS expressions

NM_000051.4:c.8307G>A
NM_000051.4(ATM):c.8307G>A (p.Trp2769Ter)
NC_000011.10:g.108343260G>A
CM000673.2:g.108343260G>A
NC_000011.9:g.108213987G>A
CM000673.1:g.108213987G>A
NC_000011.8:g.107719197G>A
NG_009830.1:g.125429G>A
NG_054724.1:g.131573C>T
ENST00000452508.7:c.8307G>A
ENST00000713593.1:c.*7778G>A
ENST00000278616.9:c.8307G>A
ENST00000638786.2:n.1005G>A
ENST00000682286.1:n.3064G>A
ENST00000682302.1:n.2725G>A
ENST00000683174.1:n.9791G>A
ENST00000683524.1:n.3531G>A
ENST00000684152.1:n.3723G>A
ENST00000684180.1:n.781G>A
ENST00000684447.1:n.4800G>A
ENST00000527805.6:c.*3371G>A
ENST00000675595.1:c.*3442G>A
ENST00000675843.1:c.8307G>A
ENST00000278616.8:c.8307G>A
ENST00000452508.6:c.8307G>A
ENST00000524755.5:c.227-7968C>T
ENST00000524792.5:n.4522G>A
ENST00000525729.5:c.641-34189C>T
ENST00000526725.1:n.272-2896C>T
ENST00000527531.5:c.*1197-7968C>T
ENST00000615746.4:c.*1197-7968C>T
NM_000051.3:c.8307G>A
NM_001330368.1:c.641-34189C>T
NM_001351110.1:c.695-7968C>T
NM_001351834.1:c.8307G>A
NR_147053.2:n.2302-7968C>T
NM_001330368.2:c.641-34189C>T
NM_001351110.2:c.695-7968C>T
NM_001351834.2:c.8307G>A
NR_147053.3:n.2300-7968C>T
More

Pathogenic

Met criteria codes 3
PM3 PVS1 PM5_Supporting
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.8307G>A (p.Trp2769*) 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 has been detected in at least 2 individuals with Ataxia-Telangiectasia (PMID: 8845835, 26896183). The highest population minor allele frequency in gnomAD v2.1.1 0.00005 in the East Asian population (PM2_Supporting, BS1, and BA1 are not met). In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant hereditary breast cancer 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)
Met criteria codes
PM3
This Variant has been detected in atleast 2 individuals with Ataxia-Telangiectasia(PMID:8845835,26896183)
PVS1
The c.8307G>A (p.Trp2769Ter) 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 (ATM p.Arg3047*), as classified by the HBOP VCEP, and is expected to be more deleterious.
Not Met criteria codes
PM2
This variant has a minor allele frequency in gnomAD v2.1.1 of 0.005% in the East Asian population which is above the threshold of 0.001% (PM2_Supporting, BS1, and BA1 are not met).
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.