ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.1272T>C (p.Pro424=) (rs35578748)

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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000159603 SCV000213198 likely benign Hereditary cancer-predisposing syndrome 2014-07-08 criteria provided, single submitter clinical testing
Color RCV000159603 SCV000537415 likely benign Hereditary cancer-predisposing syndrome 2015-07-16 criteria provided, single submitter clinical testing
GeneDx RCV000211959 SCV000209587 benign not specified 2014-09-28 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.
Illumina Clinical Services Laboratory,Illumina RCV000122817 SCV000367028 uncertain significance Ataxia-telangiectasia syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000211959 SCV000694176 likely benign not specified 2018-11-12 criteria provided, single submitter clinical testing Variant summary: ATM c.1272T>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 0.00028 in 274872 control chromosomes (gnomAD). This frequency is not significantly higher than expected for a pathogenic variant in ATM causing Ataxia-Telangiectasia (0.00028 vs 0.004), allowing no conclusion about variant significance. c.1272T>C has been reported in the literature in an individual affected with Breast Cancer (Bernstein 2010), however this report does not provide unequivocal conclusions about association of the variant with Ataxia-Telangiectasia. Co-occurrence with another pathogenic variant have been reported (ATM c.6095G>A, in an internal sample), providing supporting evidence for a benign role. In addition, the variant was reported in 4 / 7325 European American women, who were older than 70 years of age, and never had cancer (in the FLOSSIES database). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (1 classifying the variant as benign, 2 calling it likely benign, and one as a VUS). Based on the evidence outlined above, the variant was classified as likely benign.
Invitae RCV000122817 SCV000166074 benign Ataxia-telangiectasia syndrome 2017-12-29 criteria provided, single submitter clinical testing
PreventionGenetics RCV000588662 SCV000805494 likely benign not provided 2016-12-30 criteria provided, single submitter clinical testing

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