ClinVar Miner

Submissions for variant NM_000051.4(ATM):c.6338C>G (p.Thr2113Ser)

dbSNP: rs573290117
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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000221486 SCV000278223 uncertain significance Hereditary cancer-predisposing syndrome 2021-12-10 criteria provided, single submitter clinical testing The p.T2113S variant (also known as c.6338C>G), located in coding exon 42 of the ATM gene, results from a C to G substitution at nucleotide position 6338. The threonine at codon 2113 is replaced by serine, an amino acid with similar properties. This amino acid position is poorly 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.
Invitae RCV000533728 SCV000622656 uncertain significance Ataxia-telangiectasia syndrome 2024-01-19 criteria provided, single submitter clinical testing This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 2113 of the ATM protein (p.Thr2113Ser). This variant is present in population databases (rs573290117, gnomAD 0.03%). 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: 233776). 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 serine 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 RCV000221486 SCV000903052 likely benign Hereditary cancer-predisposing syndrome 2016-11-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001174836 SCV001338210 uncertain significance not specified 2020-02-24 criteria provided, single submitter clinical testing Variant summary: ATM c.6338C>G (p.Thr2113Ser) results in a conservative amino acid change located in the PIK-related kinase, FAT domain (IPR003151) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 249878 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in ATM causing Breast Cancer (4.8e-05 vs 0.001), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.6338C>G in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance (2x) and likely benign (1x). Based on the evidence outlined above, the variant was classified as uncertain significance.
KCCC/NGS Laboratory, Kuwait Cancer Control Center RCV003227722 SCV003924409 uncertain significance Familial cancer of breast 2023-05-17 criteria provided, single submitter clinical testing a variant of uncertain significance in the ATM gene (p.Thr2113Ser). This sequence change replaces threonine, which is neutral and polar, with serine, which is neutral and polar, at codon 2113 of the ATM protein (p.Thr2113Ser). This amino acid position is poorly conserved. (PhyloP=-0.14). This variant is present in population databases (rs573290117, gnomAD 0.03%). 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: 233776). In addition, this alteration is predicted to be tolerated by in silico analysis.. 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.
Natera, Inc. RCV000533728 SCV001457414 uncertain significance Ataxia-telangiectasia syndrome 2020-09-16 no assertion criteria provided clinical testing

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