Submissions for variant NM_004006.3(DMD):c.3021G>A (p.Ser1007=)

gnomAD frequency: 0.01212  dbSNP: rs1800268

Total submissions: 12

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080536	SCV000112438	benign	not specified	2014-03-31	criteria provided, single submitter	clinical testing
GeneDx	RCV000080536	SCV000168174	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000080536	SCV000268954	benign	not specified	2014-10-29	criteria provided, single submitter	clinical testing	p.Ser1007Ser in exon 23 of DMD: This variant is not expected to have clinical si gnificance because it has been identified in 1.7% (112/6728) of European America n chromosomes by the NHLBI Exome Sequencing Project (http://evs.gs.washington.ed u/EVS/; dbSNP rs1800268).
Invitae	RCV000231618	SCV000288051	benign	Duchenne muscular dystrophy	2024-02-01	criteria provided, single submitter	clinical testing
PreventionGenetics, part of Exact Sciences	RCV000080536	SCV000309928	benign	not specified		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000241805	SCV000319072	benign	Cardiovascular phenotype	2015-06-12	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.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001528752	SCV000603354	benign	not provided	2023-10-26	criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV001167431	SCV001329931	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	RCV000080536	SCV001361883	benign	not specified	2019-02-18	criteria provided, single submitter	clinical testing	Variant summary: DMD c.3021G>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 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 0.012 in 204360 control chromosomes, predominantly within the Non-Finnish European subpopulation at a frequency of 0.02 in the gnomAD database, including 11 homozygotes and 717 hemizygotes. The observed variant frequency within Non-Finnish European control individuals in the gnomAD database is approximately 1.8 fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Duchenne muscular dystrophy phenotype (0.011), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.3021G>A in individuals affected with Duchenne muscular dystrophy and no experimental evidence demonstrating its impact on protein function have been reported. Three ClinVar submissions from clinical diagnostic laboratories (evaluation after 2014) cite the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001528752	SCV001741037	likely benign	not provided		no assertion criteria provided	clinical testing
Laboratory of Diagnostic Genome Analysis, Leiden University Medical Center (LUMC)	RCV000080536	SCV001797691	benign	not specified		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826740	SCV002089003	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-04-20	no assertion criteria provided	clinical testing