Submissions for variant NM_004415.4(DSP):c.7734C>T (p.Ser2578=)

gnomAD frequency: 0.00087  dbSNP: rs28763970

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124830	SCV000168269	benign	not specified	2014-02-11	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000124830	SCV000270173	likely benign	not specified	2015-08-24	criteria provided, single submitter	clinical testing	p.Ser2578Ser in exon 24 of DSP: This variant is not expected to have clinical si gnificance because it does not alter an amino acid residue and is not located wi thin the splice consensus sequence. It has been identified in 0.2% (24/10396) of African chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broa dinstitute.org; dbSNP rs28763970).
Illumina Laboratory Services, Illumina	RCV000339026	SCV000465214	likely benign	Epidermolysis bullosa simplex due to plakophilin deficiency	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000391733	SCV000465215	likely benign	Woolly hair-skin fragility syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000309573	SCV000465216	likely benign	Arrhythmogenic right ventricular cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000348027	SCV000465217	likely benign	Lethal acantholytic epidermolysis bullosa	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV001086040	SCV000555759	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-31	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000587701	SCV000698446	benign	not provided	2016-12-12	criteria provided, single submitter	clinical testing	Variant summary: The DSP c.7734C>T (p.Ser2578Ser) variant causes a synonymous change involving a non-conserved nucleotide, which 4/5 splice prediction tools predict no significant impact on normal splicing and ESE finder predicts alterations to ESE binding, although these predictions have yet to be functionally assessed. The variant of interest was observed in the large, broad control population, ExAC, with an allele frequency of 26/121388 (1/4668), predominantly in the African cohort, 24/10396 (1/433), which significantly exceeds the estimated maximal expected allele frequency for a pathogenic DSP variant of 1/100,000. Therefore, suggesting that the variant of interest is a common polymorphism found in population(s) of African origin. The variant of interest has not been, to our knowledge, reported in affected individuals via publications. Multiple clinical diagnostic laboratories/databases cite the variant as "benign/likely benign." Therefore, the variant of interest has been classified as Benign.
Ambry Genetics	RCV000620556	SCV000736638	likely benign	Cardiovascular phenotype	2016-07-15	criteria provided, single submitter	clinical testing	This alteration is classified as likely 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.
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV000769242	SCV000900618	benign	Cardiomyopathy	2018-05-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000769242	SCV001339605	benign	Cardiomyopathy	2018-11-27	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000587701	SCV002049938	likely benign	not provided	2020-10-01	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV000587701	SCV004163056	likely benign	not provided	2022-12-01	criteria provided, single submitter	clinical testing	DSP: BP4, BP7
PreventionGenetics, part of Exact Sciences	RCV003965046	SCV004778431	likely benign	DSP-related condition	2022-08-11	criteria provided, single submitter	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Clinical Genetics, Academic Medical Center	RCV000124830	SCV001924550	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000587701	SCV001972551	likely benign	not provided		no assertion criteria provided	clinical testing