Submissions for variant NM_004006.3(DMD):c.2949+2T>C

dbSNP: rs2040709857

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Invitae	RCV001226167	SCV001398468	pathogenic	Duchenne muscular dystrophy	2023-03-18	criteria provided, single submitter	clinical testing	This sequence change affects a donor splice site in intron 22 of the DMD gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 22 and introduces a premature termination codon (PMID: 11241855). The resulting mRNA is expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 953819). Disruption of this splice site has been observed in individual(s) with Duchenne muscular dystrophy (PMID: 11241855, 19760747, 27593222). This variant is not present in population databases (gnomAD no frequency).
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV002222680	SCV002500329	likely pathogenic	Qualitative or quantitative defects of dystrophin	2022-03-11	criteria provided, single submitter	clinical testing	Variant summary: DMD c.2949+2T>C is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. One computational tool predicts the variant abolishes a 5' splicing donor site and three predict the variant has no significant impact on splicing. However, these predictions have yet to be confirmed by functional studies. The variant was absent in 183060 control chromosomes (gnomAD). To our knowledge, no occurrence of c.2949+2T>C in individuals affected with Dystrophinopathies and no experimental evidence demonstrating its impact on protein function have been reported. Two ClinVar submitters have assessed the variant since 2014: both have classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic.
GeneDx	RCV002276666	SCV002567694	pathogenic	not provided	2022-08-15	criteria provided, single submitter	clinical testing	Canonical splice site variant predicted to result in a null allele in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25007885, 16199547, 16770791)
Baylor Genetics	RCV003462772	SCV004193995	likely pathogenic	Becker muscular dystrophy	2023-05-29	criteria provided, single submitter	clinical testing
Natera, Inc.	RCV001828804	SCV002089651	likely pathogenic	Becker muscular dystrophy; Duchenne muscular dystrophy; Cardiomyopathy; Dystrophin deficiency	2020-09-29	no assertion criteria provided	clinical testing