ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6333T>C (p.His2111=) (rs55756349)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000122873 SCV000166131 likely benign Ataxia-telangiectasia syndrome 2017-12-29 criteria provided, single submitter clinical testing
Ambry Genetics RCV000162702 SCV000213159 likely benign Hereditary cancer-predisposing syndrome 2014-06-27 criteria provided, single submitter clinical testing
GeneDx RCV000433086 SCV000519058 likely benign not specified 2018-01-05 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Color RCV000162702 SCV000682326 likely benign Hereditary cancer-predisposing syndrome 2016-04-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000433086 SCV000916588 uncertain significance not specified 2018-08-13 criteria provided, single submitter clinical testing Variant summary: ATM c.6333T>C alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 5.3e-05 in 245502 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in ATM causing Breast Cancer (5.3e-05 vs 0.001), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.6333T>C in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from other clinical diagnostic laboratories (evaluation after 2014) cite the variant as "likely benign." Based on the evidence outlined above, the variant was classified as VUS-possibly benign.

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