ClinVar Miner

Submissions for variant NM_004415.4(DSP):c.8496ATCTCGCTCCGG[1] (p.2827SGSR[4]) (rs397516971)

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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 RCV000038112 SCV000061778 likely benign not specified 2015-02-18 criteria provided, single submitter clinical testing p.Ser2843_Arg2846del in exon 24 of DSP: This variant is not expected to have cli nical significance because it has been identified in 0.4% (50/11494) of Latino c hromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute .org). This in-frame deletion of four amino acids occurs within a region of repe ating amino acids. It can result from several different DNA deletions, and is pr esent in mammals (dolphin, opossum, and platypus) and other evolutionarily dista nt species.
GeneDx RCV000038112 SCV000233697 likely benign not specified 2017-08-23 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.
Invitae RCV001079689 SCV000641358 likely benign Dilated cardiomyopathy with woolly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8 2020-11-26 criteria provided, single submitter clinical testing
Molecular Diagnostic Laboratory for Inherited Cardiovascular Disease,Montreal Heart Institute RCV000845325 SCV000987371 uncertain significance not provided criteria provided, single submitter clinical testing
Color Health, Inc RCV001186904 SCV001353514 likely benign Cardiomyopathy 2018-11-09 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000038112 SCV001360929 benign not specified 2019-07-08 criteria provided, single submitter clinical testing Variant summary: DSP c.8508_8519del12 (p.Ser2843_Arg2846del) results in an in-frame deletion that is predicted to remove four amino acids from a repetitive region at the C-terminus of the protein (of note, this protein level change can be a result of several different DNA deletions). The variant allele was found at a frequency of 0.0003 in 278122 control chromosomes, predominantly at a frequency of 0.0015 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 7.5 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSP causing Arrhythmogenic Right Ventricular Dysplasia/Cardiomyopathy phenotype (0.0002), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. Though the variant has been reported in the literature in one individual affected with Arrhythmogenic Right Ventricular Cardiomyopathy (Green_2014), it was also described in a healthy control (Kapplinger_2011). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters (evaluation after 2014) classified the variant as likely benign. Based on the evidence outlined above, the variant was classified as benign.

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