ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.1505C>G (p.Ala502Gly)

gnomAD frequency: 0.00001  dbSNP: rs766595156
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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000483795 SCV000572404 uncertain significance not provided 2018-10-19 criteria provided, single submitter clinical testing This variant is denoted ATM c.1505C>G at the cDNA level, p.Ala502Gly (A502G) at the protein level, and results in the change of an Alanine to a Glycine (GCT>GGT). This variant was observed in at least one individual with lung squamous cell carcinoma (Lu 2015). ATM Ala502Gly was not observed at a significant allele frequency in large population cohorts (Lek 2016). This variant is not located within 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 Ala502Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Ambry Genetics RCV000566039 SCV000665158 uncertain significance Hereditary cancer-predisposing syndrome 2023-06-12 criteria provided, single submitter clinical testing The p.A502G variant (also known as c.1505C>G), located in coding exon 9 of the ATM gene, results from a C to G substitution at nucleotide position 1505. The alanine at codon 502 is replaced by glycine, an amino acid with similar properties. This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Labcorp Genetics (formerly Invitae), Labcorp RCV000688771 SCV000816395 uncertain significance Ataxia-telangiectasia syndrome 2024-01-18 criteria provided, single submitter clinical testing This sequence change replaces alanine, which is neutral and non-polar, with glycine, which is neutral and non-polar, at codon 502 of the ATM protein (p.Ala502Gly). This variant is present in population databases (rs766595156, gnomAD 0.007%). 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: 422834). 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.
Color Diagnostics, LLC DBA Color Health RCV000566039 SCV001347300 uncertain significance Hereditary cancer-predisposing syndrome 2023-12-05 criteria provided, single submitter clinical testing This missense variant replaces alanine with glycine at codon 502 of the ATM protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with ATM-related disorders in the literature. This variant has been identified in 1/251254 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.
Sema4, Sema4 RCV000566039 SCV002530464 uncertain significance Hereditary cancer-predisposing syndrome 2021-11-24 criteria provided, single submitter curation
Athena Diagnostics RCV000483795 SCV002771711 uncertain significance not provided 2021-08-05 criteria provided, single submitter clinical testing
Baylor Genetics RCV004568204 SCV005057167 uncertain significance Familial cancer of breast 2023-12-06 criteria provided, single submitter clinical testing
Natera, Inc. RCV000688771 SCV002095455 uncertain significance Ataxia-telangiectasia syndrome 2020-12-08 no assertion criteria provided clinical testing

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