Submissions for variant NM_004415.4(DSP):c.6351T>C (p.Asp2117=)

gnomAD frequency: 0.00019  dbSNP: rs148743859

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000150577	SCV000197836	likely benign	not specified	2012-03-19	criteria provided, single submitter	clinical testing	Asp2117Asp in exon 24 of DSP: This variant is not expected to have clinical sign ificance because it does not alter an amino acid residue and is not located with in the splice consensus sequence. It has been identified in 3/7020 European Amer ican chromosomes from a broad population by the NHLBI Exome Sequencing Project ( http://evs.gs.washington.edu/EVS; dbSNP rs148743859). Asp2117Asp in exon 24 of DSP (rs148743859; allele frequency = 0.04%, 3/7020) **
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000586587	SCV000698443	benign	not provided	2016-08-09	criteria provided, single submitter	clinical testing	Variant summary: The DSP c.6351T>C (p.Asp2117Asp) variant involves the alteration of a non-conserved nucleotide, resulting in a synonymous change. One in silico tool predicts a damaging outcome for this variant. This variant was found in 11/121018 control chromosomes, predominantly observed in the European (Non-Finnish) subpopulation at a frequency of 0.0001653 (11/66564). This frequency is about 17 times the estimated maximal expected allele frequency of a pathogenic DSP variant (0.00001), suggesting this is likely a benign polymorphism found primarily in the populations of European (Non-Finnish) origin. In addition, one clinical diagnostic laboratories/reputable databases has classified this variant as likely benign. The variant of interest has not, to our knowledge, been reported in affected individuals via publications nor evaluated for functional impact by in vivo/vitro studies. Due to the synonymous nature of this variant, the lack of predicted effect on splicing, and the relatively high frequency in the normal population, this variant is classified as benign.
GeneDx	RCV000586587	SCV000724245	likely benign	not provided	2021-02-24	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000620343	SCV000738192	likely benign	Cardiovascular phenotype	2017-10-13	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.
Invitae	RCV001083563	SCV000763491	likely benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-28	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001184988	SCV001351100	likely benign	Cardiomyopathy	2018-10-16	criteria provided, single submitter	clinical testing
CHEO Genetics Diagnostic Laboratory, Children's Hospital of Eastern Ontario	RCV001184988	SCV002043299	likely benign	Cardiomyopathy	2020-12-09	criteria provided, single submitter	clinical testing