Submissions for variant NM_004006.3(DMD):c.8762A>G (p.His2921Arg)

gnomAD frequency: 0.02191  dbSNP: rs1800279

Total submissions: 16

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080812	SCV000112714	benign	not specified	2015-03-10	criteria provided, single submitter	clinical testing
GeneDx	RCV000080812	SCV000168147	benign	not specified	2014-03-10	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	RCV000080812	SCV000268976	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	p.His2921Arg in exon 59 of DMD: This variant is not expected to have clinical si gnificance because it has been identified in 3% (200/6728) of European American chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.edu/ EVS/; dbSNP rs1800279).
PreventionGenetics, part of Exact Sciences	RCV004528101	SCV000309949	benign	DMD-related disorder	2019-05-09	criteria provided, single submitter	clinical testing	This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).
Ambry Genetics	RCV000242837	SCV000318282	benign	Cardiovascular phenotype	2015-09-23	criteria provided, single submitter	clinical testing	This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, 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	RCV000355558	SCV000482223	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.
Invitae	RCV000458193	SCV000560811	benign	Duchenne muscular dystrophy	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001529480	SCV000603333	benign	not provided	2023-10-23	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080812	SCV001364029	benign	not specified	2019-02-18	criteria provided, single submitter	clinical testing	Variant summary: DMD c.8762A>G (p.His2921Arg) results in a non-conservative amino acid change located in a spectrin repeat (IPR018159) of 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 0.026 in 200041 control chromosomes in the gnomAD database, including 42 homozygotes and 1923 hemizygotes. These data strongly suggest that the variant is benign. Six ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign (5x) and once as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Genome-Nilou Lab	RCV000458193	SCV001653414	likely benign	Duchenne muscular dystrophy	2021-05-18	criteria provided, single submitter	clinical testing
OMIM	RCV000012020	SCV000032254	uncertain significance	Becker muscular dystrophy	1994-09-01	no assertion criteria provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529480	SCV001743010	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000080812	SCV001797734	benign	not specified		no assertion criteria provided	clinical testing
Clinical Genetics, Academic Medical Center	RCV000080812	SCV001926080	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000080812	SCV001931083	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826458	SCV002080242	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-03-28	no assertion criteria provided	clinical testing