Submissions for variant NM_004415.4(DSP):c.2673T>C (p.Tyr891=)

gnomAD frequency: 0.00703  dbSNP: rs146407262

Total submissions: 18

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000038012	SCV000061678	benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	p.Tyr891Tyr in Exon 19 of DSP: This variant is not expected to have clinical sig nificance because it does not alter an amino acid residue, is not located within the splice consensus sequence and has been identified in 2.3% (87/3738) of Afri can American chromosomes from a broad population by the NHLBI Exome Sequencing P roject (http://evs.gs.washington.edu/EVS; dbSNP rs146407262).
GeneDx	RCV000038012	SCV000168260	benign	not specified	2014-01-23	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001086676	SCV000288531	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2025-01-28	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000344374	SCV000464942	likely benign	Lethal acantholytic epidermolysis bullosa	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000405620	SCV000464943	likely benign	Arrhythmogenic right ventricular cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000284266	SCV000464944	likely benign	Epidermolysis bullosa simplex due to plakophilin deficiency	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000339335	SCV000464945	likely benign	Woolly hair-skin fragility syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587575	SCV000698426	benign	not provided	2016-09-19	criteria provided, single submitter	clinical testing	Variant summary: The DSP c.2673T>C (p.Tyr891Tyr) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. 5/5 splice prediction tools predict no significant impact on normal splicing. This variant was found in 257/121370 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0239654 (249/10390). This frequency is about 959 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.000025), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. In addition, multiple clinical diagnostic laboratories have classified this variant as benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications. Taken together, this variant is classified as Benign.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769223	SCV000900599	benign	Cardiomyopathy	2017-03-07	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769223	SCV000904531	benign	Cardiomyopathy	2018-03-16	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587575	SCV001471686	benign	not provided	2021-05-22	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV003996337	SCV004821005	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma	2024-02-05	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000587575	SCV005222743	likely benign	not provided		criteria provided, single submitter	not provided
Clinical Genetics, Academic Medical Center	RCV000038012	SCV001925468	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000038012	SCV001929007	benign	not specified		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000038012	SCV001956986	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000038012	SCV001973552	benign	not specified		no assertion criteria provided	clinical testing
Cohesion Phenomics	RCV000769223	SCV003802967	benign	Cardiomyopathy	2022-09-23	no assertion criteria provided	clinical testing