ClinVar Miner

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

gnomAD frequency: 0.00077  dbSNP: rs28763971
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 18
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Biesecker Lab/Clinical Genomics Section, National Institutes of Health RCV000172750 SCV000051540 benign not specified 2013-06-24 criteria provided, single submitter research
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.
Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia RCV000202956 SCV000257973 likely benign Arrhythmogenic right ventricular cardiomyopathy 2015-05-14 criteria provided, single submitter clinical testing
Laboratory for Molecular Medicine, Mass General Brigham 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).
Invitae RCV001080914 SCV000288552 benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2024-01-31 criteria provided, single submitter clinical testing
Ambry Genetics RCV000247844 SCV000319551 benign Cardiovascular phenotype 2015-03-23 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Illumina Laboratory Services, Illumina RCV000400542 SCV000465275 benign Woolly hair-skin fragility syndrome 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Illumina Laboratory Services, Illumina RCV001095160 SCV000465276 likely benign Arrhythmogenic right ventricular dysplasia 8 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease.
Illumina Laboratory Services, Illumina RCV000342233 SCV000465277 benign Lethal acantholytic epidermolysis bullosa 2018-01-13 criteria provided, single submitter clinical testing This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV001812025 SCV000883750 benign not provided 2023-10-06 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario RCV000770253 SCV000901685 benign Cardiomyopathy 2015-11-06 criteria provided, single submitter clinical testing
Color Diagnostics, LLC DBA Color Health RCV000770253 SCV000903104 benign Cardiomyopathy 2018-06-11 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp 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.
Center for Advanced Laboratory Medicine, UC San Diego Health, University of California San Diego RCV000853001 SCV000995755 benign Long QT syndrome; Hypertrophic cardiomyopathy; Ventricular tachycardia 2019-04-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV002492463 SCV002797410 likely benign Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8; Lethal acantholytic epidermolysis bullosa; Woolly hair-skin fragility syndrome; Keratosis palmoplantaris striata 2; Cardiomyopathy, dilated, with wooly hair, keratoderma, and tooth agenesis 2021-08-03 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001812025 SCV004042250 benign not provided 2023-10-01 criteria provided, single submitter clinical testing DSP: BP4, BS1, BS2
Clinical Genetics, Academic Medical Center RCV000172750 SCV001923207 benign not specified no assertion criteria provided clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000172750 SCV001932622 benign not specified no assertion criteria provided clinical testing

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.