Submissions for variant NM_004006.3(DMD):c.2168+13T>C

gnomAD frequency: 0.32216  dbSNP: rs228373

Total submissions: 13

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080482	SCV000112384	benign	not specified	2017-04-24	criteria provided, single submitter	clinical testing
GeneDx	RCV000080482	SCV000168169	benign	not specified	2013-11-22	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	RCV000080482	SCV000268950	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	c.2168+13T>C in intron 17 of DMD: This variant is not expected to have clinical significance because it is not located within the conserved splice consensus seq uence. It has been identified in 47.4% (1816/3833) of African American chromosom es from a broad population by the NHLBI Exome Sequencing Project (http://evs.gs. washington.edu/EVS; dbSNP rs228373).
PreventionGenetics, part of Exact Sciences	RCV000080482	SCV000309925	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000320614	SCV000482271	benign	Dilated cardiomyopathy 3B	2018-01-13	criteria provided, single submitter	clinical testing	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080482	SCV000917281	benign	not specified	2018-07-12	criteria provided, single submitter	clinical testing	Variant summary: DMD c.2168+13T>C 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. The variant allele was found at a frequency of 0.32 in 82561 control chromosomes in the ExAC database, including 3112 homozygotes. The observed variant frequency is approximately 28.65 fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophiopathies phenotype (0.011), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.2168+13T>C in individuals affected with Dystrophiopathies and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811369	SCV001156887	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Invitae	RCV001510188	SCV001717159	benign	Duchenne muscular dystrophy	2024-02-01	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV000320614	SCV001876803	benign	Dilated cardiomyopathy 3B	2021-07-30	criteria provided, single submitter	clinical testing
Genome-Nilou Lab	RCV001510188	SCV001876804	benign	Duchenne muscular dystrophy	2021-07-30	criteria provided, single submitter	clinical testing
Clinical Genetics, Academic Medical Center	RCV000080482	SCV001920944	benign	not specified		no assertion criteria provided	clinical testing
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000080482	SCV001962972	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001831834	SCV002092178	benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-08-09	no assertion criteria provided	clinical testing