Submissions for variant NM_004415.4(DSP):c.2773C>T (p.Arg925Trp) (rs145933612)

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine	RCV000038015	SCV000061681	likely benign	not specified	2015-11-09	criteria provided, single submitter	clinical testing	p.Arg925Trp in exon 19 of DSP: This variant is not expected to have clinical sig nificance because it has been identified in 0.4% (45/10296) of African chromosom es by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org; db SNP rs145933612).
GeneDx	RCV000038015	SCV000233599	likely benign	not specified	2017-11-14	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.
Division of Genomic Diagnostics,The Children's Hospital of Philadelphia	RCV000238651	SCV000297155	uncertain significance	Arrhythmogenic right ventricular cardiomyopathy	2015-09-24	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000370699	SCV000464954	likely benign	Skin fragility woolly hair syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000276162	SCV000464955	likely benign	Epidermolysis bullosa, lethal acantholytic	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000238651	SCV000464956	likely benign	Arrhythmogenic right ventricular cardiomyopathy	2016-06-14	criteria provided, single submitter	clinical testing
Illumina Clinical Services Laboratory,Illumina	RCV000381091	SCV000464957	likely benign	Ectodermal dysplasia skin fragility syndrome	2016-06-14	criteria provided, single submitter	clinical testing
Invitae	RCV000473091	SCV000555781	likely benign	not provided	2019-02-06	criteria provided, single submitter	clinical testing
Color	RCV000771365	SCV000903660	likely benign	Cardiomyopathy	2018-06-05	criteria provided, single submitter	clinical testing
Integrated Genetics/Laboratory Corporation of America	RCV000038015	SCV000917293	likely benign	not specified	2017-11-21	criteria provided, single submitter	clinical testing	Variant summary: The DSP c.2773C>T (p.Arg925Trp) variant involves the alteration of a conserved nucleotide that is located in the Spectrin/alpha-actinin domain (InterPro). 4/4 in silico tools predict a damaging outcome for this variant (SNPsandGO not captured due to low reliability index). This variant was found in 140/277128 control chromosomes, including 1 homozygote, at a frequency of 0.0005052, which is approximately 51 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.00001), suggesting this variant is likely a benign polymorphism. Additionally, the variant was found in 105/24026 African control chromosomes, a frequency of 0.00437, which is approximately 437 times above the maximal expected allele frequency, suggesting it is most prevalent in this subpopulation and further supporting a benign impact of the variant. The variant has been cited in the literature without strong evidence for causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.