ClinVar Miner

Submissions for variant NM_000051.3(ATM):c.6348-8T>C (rs730881292)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000580548 SCV000682329 benign Hereditary cancer-predisposing syndrome 2016-06-28 criteria provided, single submitter clinical testing
GeneDx RCV000159621 SCV000209606 benign not specified 2014-09-26 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.
Integrated Genetics/Laboratory Corporation of America RCV000159621 SCV000918541 benign not specified 2018-04-30 criteria provided, single submitter clinical testing Variant summary: ATM c.6348-8T>C 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 0.0009 in 274672 control chromosomes, predominantly at a frequency of 0.0069 within the Latino subpopulation in the gnomAD database, including 2 homozygotes. The observed variant frequency within Latino control individuals in the gnomAD database is approximately 6.9 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 Latino origin. c.6348-8T>C has been reported in the literature in individuals affected with HBOC. These report(s) do not provide unequivocal conclusions about association of the variant with Ataxia-Telangiectasia. Co-occurrences with other pathogenic variant(s) have been reported (BRCA1 c.2090dupT, p.Glu699Argfs*13), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000204288 SCV000261916 benign Ataxia-telangiectasia syndrome 2017-12-29 criteria provided, single submitter clinical testing
PreventionGenetics RCV000159621 SCV000805598 benign not specified 2016-12-12 criteria provided, single submitter clinical testing

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