Submissions for variant NM_004415.4(DSP):c.1266+6G>T

dbSNP: rs73375345

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000037987	SCV000061653	likely benign	not specified	2012-01-10	criteria provided, single submitter	clinical testing	1266+6G>T in intron 10 of DSP: This variant is not expected to have clinical sig nificance because it has been identified in 0.5% (19/3738) of African American c hromosomes from a broad, though clinically unspecified population (NHLBI Exome S equencing Project; http://evs.gs.washington.edu/EVS). This variant is also liste d in dbSNP (rs73375345). 1266+6G>T in intron 10 of DSP (rs73375345, NHLBI Exome Seq Project; 0.5%, 19/3738)
GeneDx	RCV000037987	SCV000168255	benign	not specified	2014-03-12	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.
Invitae	RCV000467421	SCV000555769	benign	Arrhythmogenic cardiomyopathy with wooly hair and keratoderma; Arrhythmogenic right ventricular dysplasia 8	2024-01-29	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000771844	SCV000904558	benign	Cardiomyopathy	2018-10-08	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000037987	SCV000919292	benign	not specified	2018-02-05	criteria provided, single submitter	clinical testing	Variant summary: DSP c.1266+6G>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. 3/5 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 0.00065 in 276288 control chromosomes in gnomAD. The observed variant frequency is approximately 64.79 fold of the estimated maximal expected allele frequency for a pathogenic variant in DSP causing Arrhythmia phenotype (1e-05), strongly suggesting that the variant is benign. c.1266+6G>T has been reported in the literature in one individual with DCM (Pugh_2014), and was considered likley benign by the authors. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. One laboratory classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
CeGaT Center for Human Genetics Tuebingen	RCV001705680	SCV004185329	likely benign	not provided	2023-11-01	criteria provided, single submitter	clinical testing	DSP: BP4
Clinical Genetics, Academic Medical Center	RCV000037987	SCV001921058	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001705680	SCV001929284	likely benign	not provided		no assertion criteria provided	clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	RCV000037987	SCV001957984	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001705680	SCV001967882	likely benign	not provided		no assertion criteria provided	clinical testing