Submissions for variant NM_004006.3(DMD):c.357+5G>A

gnomAD frequency: 0.00013  dbSNP: rs778431187

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000698774	SCV000827460	uncertain significance	Duchenne muscular dystrophy	2025-01-17	criteria provided, single submitter	clinical testing	This sequence change falls in intron 5 of the DMD gene. It does not directly change the encoded amino acid sequence of the DMD protein. It affects a nucleotide within the consensus splice site. This variant is present in population databases (rs778431187, gnomAD 0.008%). This variant has not been reported in the literature in individuals affected with DMD-related conditions. ClinVar contains an entry for this variant (Variation ID: 576305). Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant is not likely to affect RNA splicing. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Eurofins Ntd Llc (ga)	RCV000732905	SCV000860903	uncertain significance	not provided	2018-04-24	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001332368	SCV001524676	uncertain significance	Becker muscular dystrophy	2020-06-01	criteria provided, single submitter	clinical testing	This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868].
Ambry Genetics	RCV002458270	SCV002616737	uncertain significance	Cardiovascular phenotype	2022-08-02	criteria provided, single submitter	clinical testing	The c.357+5G>A intronic variant results from a G to A substitution 5 nucleotides after coding exon 5 in the DMD gene. Based on data from gnomAD, the A allele has an overall frequency of 0.0005% (1/183181) total alleles studied, with 0 hemizygote(s) observed. The highest observed frequency was 0.0076% (1/13143) of African alleles. This nucleotide position is not well conserved in available vertebrate species. In silico splice site analysis predicts that this alteration will not have any significant effect on splicing. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Fulgent Genetics, Fulgent Genetics	RCV002477595	SCV002782593	uncertain significance	Becker muscular dystrophy; Duchenne muscular dystrophy; Dilated cardiomyopathy 3B	2022-05-11	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003330910	SCV004038118	uncertain significance	not specified	2023-08-19	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001830537	SCV002092911	uncertain significance	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2018-05-21	no assertion criteria provided	clinical testing
PreventionGenetics, part of Exact Sciences	RCV004544948	SCV004772231	likely benign	DMD-related disorder	2023-07-14	no assertion criteria provided	clinical testing	This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).