ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8605A>G (p.Ile2869Val) (rs28763971)

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Total submissions: 14
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000756042 SCV000883750 benign not provided 2018-06-04 criteria provided, single submitter clinical testing
Ambry Genetics RCV000247844 SCV000319551 benign Cardiovascular phenotype 2015-03-23 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance
Biesecker Lab/Clinical Genomics Section,National Institutes of Health RCV000172750 SCV000051540 benign not specified 2013-06-24 criteria provided, single submitter research
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000770253 SCV000901685 benign Cardiomyopathy 2015-11-06 criteria provided, single submitter clinical testing
Color RCV000770253 SCV000903104 benign Cardiomyopathy 2018-06-11 criteria provided, single submitter clinical testing
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia RCV000202956 SCV000257973 likely benign Arrhythmogenic right ventricular cardiomyopathy 2015-05-14 criteria provided, single submitter clinical testing
GeneDx RCV000172750 SCV000168273 benign not specified 2013-01-13 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 RCV000341145 SCV000465274 likely benign Ectodermal dysplasia skin fragility syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000400542 SCV000465275 likely benign Skin fragility woolly hair syndrome 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000202956 SCV000465276 likely benign Arrhythmogenic right ventricular cardiomyopathy 2016-06-14 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000342233 SCV000465277 likely benign Epidermolysis bullosa, lethal acantholytic 2016-06-14 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000172750 SCV000919285 benign not specified 2018-05-29 criteria provided, single submitter clinical testing Variant summary: DSP c.8605A>G (p.Ile2869Val) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0021 in 275770 control chromosomes, predominantly at a frequency of 0.027 within the East Asian subpopulation in the gnomAD database, including 6 homozygotes. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 1080-folds higher than the estimated maximal expected allele frequency for a pathogenic variant in DSP causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. The variant, c.8605A>G, has been reported in the literature in individuals affected with ARVC and sudden death (Bao_2013, Neubauer_2016, Suktitipat_2017, Ng_2013). These report(s) do not provide unequivocal conclusions about association of the variant with Cardiomyopathy. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple ClinVar submissions from clinical diagnostic laboratories cite the variant as "likely benign/benign." Based on the evidence outlined above, the variant was classified as benign.
Invitae RCV000231681 SCV000288552 benign Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular cardiomyopathy, type 8 2018-01-19 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000172750 SCV000269040 benign not specified 2015-03-23 criteria provided, single submitter clinical testing p.Ile2869Val in exon 24 of DSP: This variant is not expected to have clinical si gnificance because it has been identified in 2.7% (228/8370) of East Asian chrom osomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org ; dbSNP rs28763971).

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