ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.2840A>G (p.Tyr947Cys)

dbSNP: rs587779827
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000115164 SCV000149073 uncertain significance not provided 2022-01-19 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge
Ambry Genetics RCV000564185 SCV000660738 uncertain significance Hereditary cancer-predisposing syndrome 2024-09-06 criteria provided, single submitter clinical testing The p.Y947C variant (also known as c.2840A>G), located in coding exon 18 of the ATM gene, results from an A to G substitution at nucleotide position 2840. The tyrosine at codon 947 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV001854546 SCV002292716 uncertain significance Ataxia-telangiectasia syndrome 2024-05-27 criteria provided, single submitter clinical testing This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 947 of the ATM protein (p.Tyr947Cys). 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: 127359). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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.
PreventionGenetics, part of Exact Sciences RCV004549543 SCV004116041 uncertain significance ATM-related disorder 2023-08-24 criteria provided, single submitter clinical testing The ATM c.2840A>G variant is predicted to result in the amino acid substitution p.Tyr947Cys. To our knowledge, this variant has not been reported in literature. This variant is not present in a large population database (https://gnomad.broadinstitute.org/) and has been interpreted as a variant of uncertain significance in the ClinVar database (https://www.ncbi.nlm.nih.gov/clinvar/variation/127359/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.

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