Submissions for variant NM_004006.3(DMD):c.-8T>A

gnomAD frequency: 0.02450  dbSNP: rs113726961

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Eurofins Ntd Llc (ga)	RCV000080402	SCV000112304	benign	not specified	2016-01-25	criteria provided, single submitter	clinical testing
GeneDx	RCV000080402	SCV000168133	benign	not specified	2014-03-21	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	RCV000080402	SCV000268978	benign	not specified	2015-01-13	criteria provided, single submitter	clinical testing	c.-8T>A in exon 1 of DMD: This variant is not expected to have clinical signific ance because it has been identified in 7.8% (299/3833) of African American chrom osomes from a broad population by the NHLBI Exome Sequencing Project (http://evs .gs.washington.ed
PreventionGenetics, part of Exact Sciences	RCV000080402	SCV000309919	benign	not specified		criteria provided, single submitter	clinical testing
Illumina Laboratory Services, Illumina	RCV000353843	SCV000482283	benign	Dilated cardiomyopathy 3B	2018-01-12	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	RCV000080402	SCV000919271	benign	not specified	2018-07-19	criteria provided, single submitter	clinical testing	Variant summary: DMD c.-8T>A is located in the untranslated mRNA region upstream of the initiation codon. 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 0.01 in 68568 control chromosomes, predominantly at a frequency of 0.081 within the African or African-American subpopulation in the ExAC database, including 22 homozygotes. The observed variant frequency within African or African-American control individuals in the ExAC database is approximately 7-fold of the estimated maximal expected allele frequency for a pathogenic variant in DMD causing Dystrophiopathies phenotype (0.011), 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.-8T>A in individuals affected with Dystrophiopathies and no experimental evidence demonstrating its impact on protein function have been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as benign.
Athena Diagnostics	RCV000080402	SCV001143758	benign	not specified	2023-11-28	criteria provided, single submitter	clinical testing
Breakthrough Genomics, Breakthrough Genomics	RCV000991905	SCV005276057	benign	not provided		criteria provided, single submitter	not provided
Natera, Inc.	RCV001826721	SCV002093612	benign	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2017-08-09	no assertion criteria provided	clinical testing