ClinVar Miner

Submissions for variant NM_024422.6(DSC2):c.96del (p.Ala31_Cys32insTer)

dbSNP: rs397517408
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 7
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine RCV000039448 SCV000063132 likely pathogenic Arrhythmogenic right ventricular cardiomyopathy 2017-05-18 criteria provided, single submitter clinical testing proposed classification - variant undergoing re-assessment, contact laboratory
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000769504 SCV000900899 likely pathogenic Cardiomyopathy 2017-01-30 criteria provided, single submitter clinical testing
GeneDx RCV001824284 SCV002073980 likely pathogenic not provided 2023-01-13 criteria provided, single submitter clinical testing Reported in association with ARVC/D; however, at least one patient also harbored a second missense variant in the DSC2 gene and detailed clinical information was not provided (Barahona-Dussault et al., 2010; Adler et al., 2016); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed in large population cohorts (gnomAD); Reported in ClinVar (ClinVar Variant ID#46204); This variant is associated with the following publications: (PMID: 31402444, 23911551, 19863551, 26743238)
Invitae RCV001781362 SCV002228633 pathogenic Arrhythmogenic right ventricular dysplasia 11 2023-09-03 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Cys32*) in the DSC2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DSC2 are known to be pathogenic (PMID: 23911551). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with arrhythmogenic right ventricular cardiomyopathy (PMID: 19863551). ClinVar contains an entry for this variant (Variation ID: 46204). For these reasons, this variant has been classified as Pathogenic.
AiLife Diagnostics, AiLife Diagnostics RCV001824284 SCV002502759 likely pathogenic not provided 2021-10-05 criteria provided, single submitter clinical testing
Ambry Genetics RCV003338394 SCV004058117 likely pathogenic Cardiovascular phenotype 2023-09-14 criteria provided, single submitter clinical testing The c.96delC variant, located in coding exon 2 of the DSC2 gene, results from a deletion of one nucleotide at nucleotide position 96, causing a translational frameshift with a predicted alternate stop codon (p.C32*). The predicted stop codon occurs in the 5’ end of theDSC2 gene. Premature termination codons in the 5’ end of a gene have been reported to escape nonsense-mediated mRNAdecay and/or lead to re-initiation (Rivas et al. Science. 2015 May 8;348(6235):666-9; Lindeboom et al. Nat Genet. 2016 Oct;48(10):1112-8; Rhee et al. Sci Rep. 2017 May 10;7(1):1653). Direct evidence for this alteration is unavailable, however premature termination codons are typically deleterious in nature. This variant has been detected in individuals from an arrhythmogenic right ventricular cardiomyopathy cohort (Adler A et al. Circ Arrhythm Electrophysiol, 2016 Jan;9:e003440). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). Based on the majority of available evidence to date, this variant is likely to be pathogenic.
Preventiongenetics, part of Exact Sciences RCV003398606 SCV004103535 likely pathogenic DSC2-related condition 2023-01-31 criteria provided, single submitter clinical testing The DSC2 c.96delC variant is predicted to result in premature protein termination (p.Cys32*). This variant has been reported in individuals with arrhythmogenic right ventricular dysplasia and cardiomyopathy (Barahona-Dussault et al. 2010. PubMed ID: 19863551; Ye et al. 2019. PubMed ID: 31402444). This variant has not been reported in a large population database (http://gnomad.broadinstitute.org), indicating this variant is rare. Early termination variants in DSC2 are expected to be pathogenic. This variant is interpreted as likely pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.