ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6313A>G (p.Arg2105Gly)

dbSNP: rs879253983
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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000236852 SCV000293063 uncertain significance not provided 2016-02-19 criteria provided, single submitter clinical testing This variant is denoted ATM c.6313A>G at the cDNA level, p.Arg2105Gly (R2105G) at the protein level, and results in the change of an Arginine to a Glycine (AGG>GGG). This variant has not, to our knowledge, been published in the literature as pathogenic or benign. ATM Arg2105Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. Since Arginine and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. ATM Arg2105Gly occurs at a position that is conserved across species and is located in the FAT domain (Tavtigian 2009, Stracker 2013). In silico analyses predict that this variant is probably damaging to protein structure and function. Based on currently available information, it is unclear whether ATM Arg2105Gly is pathogenic or benign. We consider it to be a variant of uncertain significance.
Labcorp Genetics (formerly Invitae), Labcorp RCV000471131 SCV000546944 uncertain significance Ataxia-telangiectasia syndrome 2023-02-23 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 2105 of the ATM protein (p.Arg2105Gly). 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: 245884). 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.
Ambry Genetics RCV000570295 SCV000660782 uncertain significance Hereditary cancer-predisposing syndrome 2023-09-04 criteria provided, single submitter clinical testing The p.R2105G variant (also known as c.6313A>G), located in coding exon 42 of the ATM gene, results from an A to G substitution at nucleotide position 6313. The arginine at codon 2105 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly 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.
Baylor Genetics RCV004567774 SCV005056988 uncertain significance Familial cancer of breast 2024-02-15 criteria provided, single submitter clinical testing
Natera, Inc. RCV000471131 SCV002083418 uncertain significance Ataxia-telangiectasia syndrome 2021-02-02 no assertion criteria provided clinical testing

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