ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2075G>A (p.Arg692His)

gnomAD frequency: 0.00001  dbSNP: rs751515818
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV000228332 SCV000282887 uncertain significance Ataxia-telangiectasia syndrome 2022-09-28 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 692 of the ATM protein (p.Arg692His). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with ATM-related conditions. ClinVar contains an entry for this variant (Variation ID: 236682). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. 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.
Ambry Genetics RCV001014336 SCV001175033 likely benign Hereditary cancer-predisposing syndrome 2023-12-09 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.
Color Diagnostics, LLC DBA Color Health RCV001014336 SCV001344968 uncertain significance Hereditary cancer-predisposing syndrome 2019-03-01 criteria provided, single submitter clinical testing
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003343712 SCV004046894 uncertain significance Familial cancer of breast 2023-10-24 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 692 of the ATM protein (p.Arg692His). This variant is not present in population databases (gnomAD no frequency).This variant was reported in 1/60,466 breast cancer cases and in 0/53,461 controls (Dorling et al. N Engl J Med. 2021 02;384:428-439). ClinVar contains an entry for this variant (Variation ID: 236682). This amino acid position is not well conserved (PhyloP=-0.1) . In addition, this alteration is predicted to be tolerated by in silico analysis. 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
Revvity Omics, Revvity RCV000228332 SCV004234540 uncertain significance Ataxia-telangiectasia syndrome 2023-06-19 criteria provided, single submitter clinical testing
Natera, Inc. RCV000228332 SCV002084149 uncertain significance Ataxia-telangiectasia syndrome 2021-08-30 no assertion criteria provided clinical testing

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