Submissions for variant NM_004006.3(DMD):c.8734A>G (p.Asn2912Asp)

gnomAD frequency: 0.02976  dbSNP: rs1800278

Total submissions: 17

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080811	SCV000112713	benign	not specified	2014-08-08	criteria provided, single submitter	clinical testing
GeneDx	RCV000080811	SCV000168146	benign	not specified	2014-01-17	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	RCV000080811	SCV000268975	benign	not specified	2015-03-21	criteria provided, single submitter	clinical testing	p.Asn2912Asp in exon 59 of DMD: This variant is not expected to have clinical si gnificance because it has been identified in 7.6% (802/10506) of African chromos omes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitute.org/; dbSNP rs1800278).
PreventionGenetics, part of Exact Sciences	RCV000080811	SCV000309948	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000242355	SCV000318156	benign	Cardiovascular phenotype	2015-10-23	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	RCV000264708	SCV000482224	likely benign	Dilated cardiomyopathy 3B	2017-04-27	criteria provided, single submitter	clinical testing	This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Invitae	RCV000012019	SCV000560840	benign	Duchenne muscular dystrophy	2024-02-01	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000711470	SCV000603355	benign	not provided	2023-11-29	criteria provided, single submitter	clinical testing
Phosphorus, Inc.	RCV000012019	SCV000679896	benign	Duchenne muscular dystrophy	2017-08-01	criteria provided, single submitter	clinical testing
Athena Diagnostics Inc	RCV000711470	SCV000841838	benign	not provided	2017-09-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000080811	SCV001360766	benign	not specified	2019-03-07	criteria provided, single submitter	clinical testing	Variant summary: DMD c.8734A>G (p.Asn2912Asp) results in a conservative amino acid change located in in a spectrin/alpha-actinin repeat (IPR018159) of the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.022 in 200085 control chromosomes in the gnomAD database, including 59 homozygotes and 1416 hemizygotes. The observed variant frequency is significantly higher than expected for a pathogenic variant in DMD causing Dystrophinopathies phenotype, strongly suggesting that the variant is benign. Seven ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign (6x) and once as likely benign. Based on the evidence outlined above, the variant was classified as benign.
Pars Genome Lab	RCV000012019	SCV001736777	benign	Duchenne muscular dystrophy	2021-05-18	criteria provided, single submitter	clinical testing
OMIM	RCV000012019	SCV000032253	uncertain significance	Duchenne muscular dystrophy	1994-09-01	no assertion criteria provided	literature only
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV000080811	SCV001740119	benign	not specified		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000080811	SCV001798109	benign	not specified		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV000080811	SCV001928939	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001831563	SCV002080247	benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2019-08-02	no assertion criteria provided	clinical testing