ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6367A>G (p.Ser2123Gly)

gnomAD frequency: 0.00001  dbSNP: rs876659773
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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 RCV000219988 SCV000276588 likely benign Hereditary cancer-predisposing syndrome 2024-01-12 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.
Labcorp Genetics (formerly Invitae), Labcorp RCV000627902 SCV000748786 uncertain significance Ataxia-telangiectasia syndrome 2023-10-13 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with glycine, which is neutral and non-polar, at codon 2123 of the ATM protein (p.Ser2123Gly). 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: 232449). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Not Available"; PolyPhen-2: "Benign"; Align-GVGD: "Not Available". The glycine 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.
Color Diagnostics, LLC DBA Color Health RCV000219988 SCV000904833 uncertain significance Hereditary cancer-predisposing syndrome 2019-02-02 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV001818534 SCV002066785 uncertain significance not specified 2021-01-06 criteria provided, single submitter clinical testing DNA sequence analysis of the ATM gene demonstrated a sequence change, c.6367A>G, in exon 44 that results in an amino acid change, p.Ser2123Gly. This sequence change is absent from known population databases (gnomAD). The p.Ser2123Gly change affects a poorly conserved amino acid residue located in a domain of the ATM protein that is known to be functional. The p.Ser2123Gly substitution appears to be benign using several in-silico pathogenicity prediction tools (SIFT, PolyPhen2, Align GVGD, REVEL). This variant has not been reported in the literature in individuals with ATM-related disease Due to the lack of sufficient evidences the clinical significance of the p.Ser2123Gly change remains unknown at this time.
Natera, Inc. RCV000627902 SCV002083484 uncertain significance Ataxia-telangiectasia syndrome 2020-11-09 no assertion criteria provided clinical testing

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