Submissions for variant NM_004006.3(DMD):c.2386G>A (p.Val796Ile)

gnomAD frequency: 0.00023  dbSNP: rs139726281

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000542994	SCV000625868	benign	Duchenne muscular dystrophy	2025-01-30	criteria provided, single submitter	clinical testing
GeneDx	RCV001529358	SCV000729565	benign	not provided	2021-04-28	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV001529358	SCV001158907	benign	not provided	2023-10-26	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002453401	SCV002737069	benign	Cardiovascular phenotype	2018-05-30	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.
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV004017392	SCV004847931	likely benign	not specified	2021-09-24	criteria provided, single submitter	clinical testing	The p.Val796Ile variant in DMD is classified as likely benign because it has been identified in 0.11% (9/7571) of Ashkenazi Jewish chromosomes, including 4 hemizygotes, and 0.04% (38/88451) of European chromosomes, include 15 hemizygotes, by gnomAD (http://gnomad.broadinstitute.org). Additionally, computational prediction tools and conservation analyses predict that this variant does not impact the protein. ACMG/AMP Criteria applied: BS1, BP4.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV004017392	SCV005423277	likely benign	not specified	2024-10-15	criteria provided, single submitter	clinical testing	Variant summary: DMD c.2386G>A (p.Val796Ile) results in a conservative amino acid change in 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 0.00024 in 176544 control chromosomes. The observed variant frequency is approximately 22 fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophinopathies phenotype (1.1e-05). c.2386G>A has been reported in the literature in individuals affected with Dystrophinopathies as a benign change (Burstein_2021). These report(s) do not provide unequivocal conclusions about association of the variant with Dystrophinopathies. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication has been ascertained in the context of this evaluation (PMID: 32746448). ClinVar contains an entry for this variant (Variation ID: 94509). Based on the evidence outlined above, the variant was classified as likely benign.
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	RCV001529358	SCV001742655	likely benign	not provided		no assertion criteria provided	clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht	RCV001529358	SCV001926850	likely benign	not provided		no assertion criteria provided	clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	RCV001529358	SCV001974257	likely benign	not provided		no assertion criteria provided	clinical testing
Natera, Inc.	RCV001826734	SCV002089736	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-11-13	no assertion criteria provided	clinical testing