ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2492A>G (p.Asp831Gly)

gnomAD frequency: 0.00001  dbSNP: rs587781352
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000166878 SCV000217694 likely benign Hereditary cancer-predisposing syndrome 2024-02-06 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV000474811 SCV000546910 uncertain significance Ataxia-telangiectasia syndrome 2022-10-24 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 831 of the ATM protein (p.Asp831Gly). This variant is present in population databases (rs587781352, gnomAD no frequency). This missense change has been observed in individual(s) with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 187178). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
GeneDx RCV000478109 SCV000570144 uncertain significance not provided 2023-07-21 criteria provided, single submitter clinical testing Not observed at a significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 28135145, 35893033)
Color Diagnostics, LLC DBA Color Health RCV000166878 SCV000904594 uncertain significance Hereditary cancer-predisposing syndrome 2022-10-10 criteria provided, single submitter clinical testing This missense variant replaces aspartic acid with glycine at codon 831 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. In a large international case-control study, this variant was reported in 3/60466 breast cancer cases and 1/53461 controls (PMID: 33471991). This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). This variant has been identified in 1/251388 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Mendelics RCV000474811 SCV001138474 uncertain significance Ataxia-telangiectasia syndrome 2019-05-28 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002498828 SCV002814026 uncertain significance Familial cancer of breast; Ataxia-telangiectasia syndrome 2021-07-28 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003315416 SCV004015194 uncertain significance Familial cancer of breast 2023-07-07 criteria provided, single submitter clinical testing This sequence change replaces aspartic acid with glycine at codon 831 of the ATM protein (p.Asp831Gly). The aspartic acid residue is weakly conserved and there is a moderate physicochemical difference between aspartic acid and glycine. This variant is present in population databases (rs587781352, ExAC <0.01%). This variant has been reported in an individual affected with colorectal cancer (PMID: 28135145). ClinVar contains an entry for this variant (Variation ID: 187178). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Baylor Genetics RCV003315416 SCV004207761 uncertain significance Familial cancer of breast 2024-03-21 criteria provided, single submitter clinical testing
Natera, Inc. RCV000474811 SCV002077874 uncertain significance Ataxia-telangiectasia syndrome 2020-09-24 no assertion criteria provided clinical testing

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. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.