Submissions for variant NM_004006.3(DMD):c.6322C>T (p.Arg2108Cys)

gnomAD frequency: 0.00981  dbSNP: rs16990169

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000080695	SCV000235819	benign	not specified	2014-08-06	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	RCV000080695	SCV000268966	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.Arg2108Cys in exon 44 of DMD: This variant is not expected to have clinical si gnificance because it has been identified in 3.3% (125/3833) of African American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu /EVS/; dbSNP rs16990169).
Invitae	RCV000227861	SCV000288064	benign	Duchenne muscular dystrophy	2024-01-31	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000243719	SCV000317913	benign	Cardiovascular phenotype	2015-09-09	criteria provided, single submitter	clinical testing	This alteration is classified as 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.
Illumina Laboratory Services, Illumina	RCV000279099	SCV000482236	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001811373	SCV001474037	benign	not provided	2023-10-02	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080695	SCV001623297	benign	not specified	2021-04-18	criteria provided, single submitter	clinical testing	Variant summary: DMD c.6322C>T (p.Arg2108Cys) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.0029 in 181372 control chromosomes in the gnomAD database, including 4 homozygotes. The observed variant frequency is approximately 267 fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophinopathies phenotype (1.1e-05), strongly suggesting that the variant is benign. To our knowledge, no occurrence of c.6322C>T in individuals affected with Dystrophinopathies and no experimental evidence demonstrating its impact on protein function have been reported. Five 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. Based on the evidence outlined above, the variant was classified as benign.
Fulgent Genetics, Fulgent Genetics	RCV002490701	SCV002797359	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Dilated cardiomyopathy 3B	2022-01-21	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001831865	SCV002091014	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-04-20	no assertion criteria provided	clinical testing