ClinVar Miner

Submissions for variant NM_001943.5(DSG2):c.1652-12C>T (rs140850369)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000037269 SCV000060926 likely benign not specified 2012-04-25 criteria provided, single submitter clinical testing 1652-12C>T in Intron 11 of DSG2: This variant is not expected to have clinical s ignificance because it has been identified in 0.4% (13/3106) of African American chromosomes from a broad population by the NHLBI Exome Sequencing Project (http ://evs.gs.washington.edu/EVS; dbSNP rs140850369). 1652-12C>T in intron 11 of DS G2 (rs140850369, allele frequency = 0.4%, 13/3106)
GeneDx RCV000037269 SCV000168240 benign not specified 2014-05-29 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 RCV001127624 SCV001286957 benign Arrhythmogenic right ventricular cardiomyopathy, type 10 2017-05-16 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases was too high to be consistent with this variant causing disease. Therefore, this variant is classified as benign.
Color Health, Inc RCV001186905 SCV001353515 benign Cardiomyopathy 2018-11-14 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000037269 SCV001623424 benign not specified 2021-05-10 criteria provided, single submitter clinical testing Variant summary: DSG2 c.1652-12C>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. 4/4 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 0.0004 in 248862 control chromosomes, predominantly at a frequency of 0.0052 within the African or African-American subpopulation in the gnomAD database, including 1 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 21 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSG2 causing Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy phenotype (0.00025), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1652-12C>T in individuals affected with Arrhythmogenic Right Ventricular Dysplasia/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. Both laboratories classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001529425 SCV001742864 likely benign not provided no assertion criteria provided clinical testing

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