ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6323A>G (p.Gln2108Arg) (rs773891864)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000163479 SCV000214034 uncertain significance Hereditary cancer-predisposing syndrome 2016-11-10 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient evidence
Invitae RCV000476875 SCV000547022 uncertain significance Ataxia-telangiectasia syndrome 2018-09-05 criteria provided, single submitter clinical testing This sequence change replaces glutamine with arginine at codon 2108 of the ATM protein (p.Gln2108Arg). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and arginine. This variant is present in population databases (rs773891864, ExAC 0.003%). This variant has not been reported in the literature in individuals with ATM-related disease. ClinVar contains an entry for this variant (Variation ID: 184258). 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.
GeneDx RCV000486607 SCV000570132 uncertain significance not provided 2018-04-16 criteria provided, single submitter clinical testing This variant is denoted ATM c.6323A>G at the cDNA level, p.Gln2108Arg (Q2108R) at the protein level, and results in the change of a Glutamine to an Arginine (CAG>CGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Gln2108Arg was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is located within the FAT domain (Stracker 2013). 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 Gln2108Arg is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color RCV000163479 SCV000682323 uncertain significance Hereditary cancer-predisposing syndrome 2018-08-07 criteria provided, single submitter clinical testing

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