Submissions for variant NM_004415.4(DSP):c.1702-18C>T

gnomAD frequency: 0.00594  dbSNP: rs148417566

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000029677	SCV000052329	benign	not specified	2019-09-16	criteria provided, single submitter	clinical testing	Variant summary: DSP c.1702-18C>T alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.0013 in 251114 control chromosomes, predominantly at a frequency of 0.019 within the African or African-American subpopulation in the gnomAD database, including 5 homozygotes. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 760-folds over the estimated maximal expected allele frequency for a pathogenic variant in DSP causing Cardiomyopathy phenotype (2.5e-05), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.1702-18C>T in individuals affected with Cardiomyopathy and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001636607	SCV001472677	benign	not provided	2023-03-28	criteria provided, single submitter	clinical testing
GeneDx	RCV001636607	SCV001848999	benign	not provided	2015-03-03	criteria provided, single submitter	clinical testing
Invitae	RCV002054491	SCV002414696	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-31	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000029677	SCV001917156	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV000029677	SCV001966535	benign	not specified		no assertion criteria provided	clinical testing