ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.2127T>C (p.Ile709=) (rs56252953)

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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 RCV000123727 SCV000213052 likely benign Hereditary cancer-predisposing syndrome 2014-07-03 criteria provided, single submitter clinical testing
Color RCV000123727 SCV000682029 benign Hereditary cancer-predisposing syndrome 2015-04-14 criteria provided, single submitter clinical testing
GeneDx RCV000211973 SCV000167070 benign not specified 2013-12-31 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 RCV000122831 SCV000367032 uncertain significance Ataxia-telangiectasia syndrome 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000211973 SCV000918556 benign not specified 2018-08-03 criteria provided, single submitter clinical testing Variant summary: ATM c.2127T>C (p.Ile709Ile) alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 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 0.0013 in 275790 control chromosomes, predominantly at a frequency of 0.019 within the East Asian subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 18.99 fold of the estimated maximal expected allele frequency for a pathogenic variant in ATM causing Breast Cancer phenotype (0.001), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. To our knowledge, no occurrence of c.2127T>C in individuals affected with Breast Cancer and no experimental evidence demonstrating its impact on protein function have been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000122831 SCV000166088 benign Ataxia-telangiectasia syndrome 2017-12-29 criteria provided, single submitter clinical testing
True Health Diagnostics RCV000123727 SCV000787850 likely benign Hereditary cancer-predisposing syndrome 2017-10-26 no assertion criteria provided clinical testing

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