ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6776C>G (p.Ser2259Cys)

dbSNP: rs786202094
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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 RCV000164736 SCV000215408 uncertain significance Hereditary cancer-predisposing syndrome 2024-05-23 criteria provided, single submitter clinical testing The p.S2259C variant (also known as c.6776C>G), located in coding exon 45 of the ATM gene, results from a C to G substitution at nucleotide position 6776. The serine at codon 2259 is replaced by cysteine, an amino acid with dissimilar properties. This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.
Color Diagnostics, LLC DBA Color Health RCV000164736 SCV001358590 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-25 criteria provided, single submitter clinical testing This missense variant replaces serine with cysteine at codon 2259 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 not been identified 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.
GeneDx RCV001770125 SCV001994639 uncertain significance not provided 2021-03-01 criteria provided, single submitter clinical testing Not observed in large population cohorts (Lek et al., 2016); In silico analysis supports that this missense variant does not alter protein structure/function; Reported in a control individual in breast, prostate, and colorectal cancer case-control studies recruited through the BioBank Japan registry (Momozawa 2018, Mizukami 2020, Fujita 2020); This variant is associated with the following publications: (PMID: 32980694, 30287823, 33309985)
Labcorp Genetics (formerly Invitae), Labcorp RCV003607250 SCV004538840 uncertain significance Ataxia-telangiectasia syndrome 2023-12-12 criteria provided, single submitter clinical testing This sequence change replaces serine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 2259 of the ATM protein (p.Ser2259Cys). 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: 185334). 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.

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