ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.5543A>G (p.Asp1848Gly)

dbSNP: rs1555107329
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000561120 SCV000672697 uncertain significance Hereditary cancer-predisposing syndrome 2021-09-16 criteria provided, single submitter clinical testing The p.D1848G variant (also known as c.5543A>G), located in coding exon 36 of the ATM gene, results from an A to G substitution at nucleotide position 5543. The aspartic acid at codon 1848 is replaced by glycine, an amino acid with similar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
St. Jude Molecular Pathology, St. Jude Children's Research Hospital RCV001526805 SCV001737439 uncertain significance Ataxia-telangiectasia syndrome 2021-04-22 criteria provided, single submitter clinical testing The ATM c.5543A>G (p.Asp1848Gly) missense change is absent in gnomAD v2.1.1 (PM2_supporting; https://gnomad.broadinstitute.org/). In silico tools are not in agreement about the effect of this variant on protein function, and to our knowledge functional assays have not been performed. This variant has not been reported in individuals with ataxia telangiectasia or breast cancer (literature review, internal data). In summary, this variant meets criteria to be classified as of uncertain significance based on the ACMG/AMP criteria: PM2.
GeneDx RCV001764680 SCV001998395 uncertain significance not provided 2019-11-20 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek 2016); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; Has not been previously published as pathogenic or benign to our knowledge
Labcorp Genetics (formerly Invitae), Labcorp RCV001526805 SCV002117388 uncertain significance Ataxia-telangiectasia syndrome 2023-08-11 criteria provided, single submitter clinical testing 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 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. ClinVar contains an entry for this variant (Variation ID: 485220). This variant has not been reported in the literature in individuals affected with ATM-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 1848 of the ATM protein (p.Asp1848Gly).
Baylor Genetics RCV003465256 SCV004207506 uncertain significance Familial cancer of breast 2023-10-19 criteria provided, single submitter clinical testing

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