Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Athena Diagnostics | RCV000201191 | SCV000255716 | pathogenic | Duchenne muscular dystrophy | 2013-10-21 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000201191 | SCV001215811 | pathogenic | Duchenne muscular dystrophy | 2021-01-14 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 21 of the DMD gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed to be hemizygous in individuals affected with Duchenne or Becker muscular dystrophy (PMID: 15351422, 27593222). ClinVar contains an entry for this variant (Variation ID: 217190). Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DMD are known to be pathogenic (PMID: 16770791, 25007885). For these reasons, this variant has been classified as Pathogenic. |
| Revvity Omics, |
RCV001781594 | SCV002021690 | pathogenic | not provided | 2021-02-23 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002222440 | SCV002500152 | pathogenic | Qualitative or quantitative defects of dystrophin | 2022-03-01 | criteria provided, single submitter | clinical testing | Variant summary: DMD c.2804-2A>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. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 3 acceptor site. At least one publication reports experimental evidence that this variant affects mRNA splicing (Deburgrave_2007). The variant was absent in 182614 control chromosomes (gnomAD). c.2804-2A>C has been reported in the literature in individuals affected with Duchenne Muscular Dystrophy (Tuffery-Giraud_2004, Deburgrave_2007, Cho_2017). These data indicate that the variant may be associated with disease. Two ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |