ClinVar Miner

Submissions for variant NM_014000.2(VCL):c.3258+10A>T (rs71579379)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769119 SCV000900493 likely benign Cardiomyopathy 2017-09-29 criteria provided, single submitter clinical testing
GeneDx RCV000038826 SCV000169785 benign not specified 2014-02-18 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 RCV000286361 SCV000364946 uncertain significance Dilated Cardiomyopathy, Dominant 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000038826 SCV000920337 benign not specified 2018-03-26 criteria provided, single submitter clinical testing Variant summary: VCL c.3258+10A>T 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. 4/5 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 0.0027 in 217628 control chromosomes, predominantly within the Non-Finnish European subpopulation at a frequency of 0.0045 in the gnomAD database, including 1 homozygote. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 180 fold above the estimated maximal expected allele frequency for a pathogenic variant in VCL causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of Non-Finnish European origin. To our knowledge, no occurrence of c.3258+10A>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign/likely benign, and one laboratory classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000229791 SCV000289916 benign Dilated cardiomyopathy 1W 2017-12-27 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000038826 SCV000062504 benign not specified 2011-12-13 criteria provided, single submitter clinical testing 3258+10A>T in Intron 21 of VCL: This variant is not expected to have clinical si gnificance because it is not located within the splice consensus sequence and ha s been identified in 0.4% (28/7018) of European American chromosomes from a broa d population by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu /EVS; dbSNP rs71579379).

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