ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.7744A>G (p.Arg2582Gly) (rs750224234)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000484994 SCV000569977 uncertain significance not provided 2018-09-20 criteria provided, single submitter clinical testing This variant is denoted ATM c.7744A>G at the cDNA level, p.Arg2582Gly (R2582G) at the protein level, and results in the change of an Arginine to a Glycine (AGA>GGA). This variant was observed in an individual with nasopharyngeal carcinoma (Chow 2017). ATM Arg2582Gly was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located in a known functional domain. In silico analysis, which includes protein predictors and evolutionary conservation, supports that this variant does not alter protein structure/function. Based on currently available evidence, it is unclear whether ATM Arg2582Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Invitae RCV000529781 SCV000622773 uncertain significance Ataxia-telangiectasia syndrome 2018-12-06 criteria provided, single submitter clinical testing This sequence change replaces arginine with glycine at codon 2582 of the ATM protein (p.Arg2582Gly). The arginine residue is moderately conserved and there is a moderate physicochemical difference between arginine and glycine. This variant is present in population databases (rs750224234, ExAC 0.01%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 420940). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C45"). 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 RCV000576036 SCV000665306 uncertain significance Hereditary cancer-predisposing syndrome 2017-01-05 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Color RCV000576036 SCV000905159 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-25 criteria provided, single submitter clinical testing

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