Submissions for variant NM_004006.3(DMD):c.2380+11G>A

gnomAD frequency: 0.00195  dbSNP: rs183120304

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000124733	SCV000168170	benign	not specified	2014-05-09	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.
Eurofins Ntd Llc (ga)	RCV000124733	SCV000339818	benign	not specified	2016-02-24	criteria provided, single submitter	clinical testing
Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine	RCV000124733	SCV000711602	benign	not specified	2014-11-24	criteria provided, single submitter	clinical testing	2380+11G>A in intron 19 of DMD: This variant is not expected to have clinical si gnificance because it is not located within the conserved splice consensus seque nce. It has been identified in 0.8% (30/3833) of African American chromosomes fr om a broad population by the NHLBI Exome Sequencing Project (http://evs.gs.washi ngton.edu/EVS; dbSNP rs183120304).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000124733	SCV001339231	benign	not specified	2020-03-30	criteria provided, single submitter	clinical testing	Variant summary: DMD c.2380+11G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 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 0.00067 in 173804 control chromosomes, predominantly at a frequency of 0.0082 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is significantly higher than the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophinopathies phenotype (0.000008824), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. To our knowledge, no occurrence of c.2380+11G>A in individuals affected with Dystrophinopathies and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and classified the variant as benign. Based on the evidence outlined above, the variant was classified as benign.
Invitae	RCV002055523	SCV002414229	benign	Duchenne muscular dystrophy	2024-01-31	criteria provided, single submitter	clinical testing
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV003736590	SCV004562290	benign	not provided	2023-09-21	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001831920	SCV002089740	likely benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2018-01-10	no assertion criteria provided	clinical testing