Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_000051.4(ATM):c.8494C>T (p.Arg2832Cys)

Curation Version - 1.0
Curation History
JSON LD for Version 1.0

CA287019

127459 (ClinVar)

Gene: ATM

Condition: hereditary breast cancer

Inheritance Mode: Autosomal dominant inheritance

Link to MONDO

UUID: a1f4fda0-ab77-4c22-a6be-6dc2f95f8e60

Approved on: 2024-01-25

Published on: 2024-02-14

HGVS expressions

NM_000051.4:c.8494C>T

NM_000051.4(ATM):c.8494C>T (p.Arg2832Cys)

NC_000011.10:g.108345818C>T

CM000673.2:g.108345818C>T

NC_000011.9:g.108216545C>T

CM000673.1:g.108216545C>T

NC_000011.8:g.107721755C>T

NG_009830.1:g.127987C>T

NG_054724.1:g.129015G>A

ENST00000452508.7:c.8494C>T

ENST00000713593.1:c.*7965C>T

ENST00000278616.9:c.8494C>T

ENST00000638786.2:n.1192C>T

ENST00000682286.1:n.3251C>T

ENST00000682302.1:n.2912C>T

ENST00000683174.1:n.9978C>T

ENST00000683524.1:n.3718C>T

ENST00000684152.1:n.3910C>T

ENST00000684180.1:n.968C>T

ENST00000684447.1:n.4987C>T

ENST00000527805.6:c.*3558C>T

ENST00000675595.1:c.*3629C>T

ENST00000675843.1:c.8494C>T

ENST00000278616.8:c.8494C>T

ENST00000452508.6:c.8494C>T

ENST00000524755.5:c.227-10526G>A

ENST00000524792.5:n.4709C>T

ENST00000525729.5:c.641-36747G>A

ENST00000526725.1:n.272-5454G>A

ENST00000527531.5:c.*1196+9097G>A

ENST00000615746.4:c.*1196+9097G>A

NM_000051.3:c.8494C>T

NM_001330368.1:c.641-36747G>A

NM_001351110.1:c.695-10526G>A

NM_001351834.1:c.8494C>T

NR_147053.2:n.2301+9097G>A

NM_001330368.2:c.641-36747G>A

NM_001351110.2:c.695-10526G>A

NM_001351834.2:c.8494C>T

NR_147053.3:n.2299+9097G>A

Likely Pathogenic

PM3_Strong PS3_Supporting PP3

PM2

Evidence Links 0

Expert Panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

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 1.2.0

Criteria Specification Approval History

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Hereditary Breast, Ovarian and Pancreatic Cancer VCEP

The c.8494C>T variant in ATM is a missense variant predicted to cause substitution of arginine by cysteine at amino acid 2832 (p.Arg2832Cys). This variant has been detected in at least 3 individuals with Ataxia-Telangiectasia (PMID: 26896183, 22017321, 26846839). The highest minor allele frequency in gnomAD v2.1.1 of 0.01% (2/16244 alleles) in the African/African American population (PM2_Supporting, BS1, and BA1 are not met). The computational predictor, Revel (Score: 0.83), predicts a damaging effect on ATM function. Additionally, experimental studies showed that this variant has impact on ATM kinase activity and protein levels but radiosensitivity was found to be intermediate compared to wild type (PMID: 18634022). In summary, this variant meets criteria to be classified as likely pathogenic for autosomal dominant hereditary breast cancer and autosomal recessive Ataxia-Telangiectasia based on the ACMG/AMP criteria applied, as specified by the HBOP VCEP. (PM3_Strong, PP3, PS3_supporting)

PM3_Strong

This variant has been detected in atleast 3 individuals with Ataxia-Telangiectasia.( PMID: 26896183, 22017321, 26846839)

PS3_Supporting

Experimental studies showed that this variant has impact on ATM kinase activity and protein levels but radiosensitivity was found to be intermediate compared to wild type

PP3

REVEL predicted the score of 0.83 which is above thresholds defined by the HBOP VCEP for PP3

PM2

This variant has a minor allele frequency in gnomAD v2.1.1 of 0.01% (2/16244 alleles) in the African/African American population (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.