Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001280610 | SCV001467824 | pathogenic | Qualitative or quantitative defects of dystrophin | 2020-12-10 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the deletion of exon 45 in the DMD gene. A presumed nomenclature of c.(6438+1_6439-1)_(6614+1_6615-1)del has been designated for the purposes of this classification. Although exact breakpoints of this deletion are not known, it is expected to result in a frameshift deletion change in the DMD gene, a known mechanism of disease. The variant was absent in 15853 control chromosomes (gnomAD, Structural Variants dataset). Deletion of exon 45 has been reported in the literature in multiple individuals affected with Dystrophinopathies (e.g. Prior_2005, Flanigan_2009, Chen_2014, Zamani_2015). These data indicate that the variant is very likely to be associated with disease. Experimental evidence demonstrated that this variant may affect mRNA splicing causing skipping of exon 44 and resulting in an in-frame product with deletion of both exons 44 and 45 (e.g. Dwianingsih_2014). Three ClinVar submitters (evaluation after 2014) cite the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic. |