Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001269239 | SCV001448559 | likely benign | not specified | 2022-12-15 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the duplication of exon 13 in the DMD gene. A presumed nomenclature of c.(1482+1_1483-1)_(1602+1_1603-1)dup has been designated for the purposes of this classification. It has been assumed that this is a tandem duplication in direct orientation (Richardson_GIM_2018, Newman_AJHG_2015). Although exact breakpoints of this duplication are not known, it is expected to result in an in-frame duplication, resulting in the insertion of 40 amino acids into spectrin repeat 2 in the central rod domain (UniProt) of the DMD gene. A large duplication variant (size: 26,434 bp) encompassing exon 13 is reported in 18 / 15814 alleles, including 17 hemizygotes in the gnomAD database, structural variants dataset. The highest variant frequency is reported within the African or African-American subpopulation (10 hemizygotes), strongly suggesting that the variant is a benign polymorphism. To our knowledge, no occurrence of c.(1482+1_1483-1)_(1602+1_1603-1)dup in individuals affected with Dystrophinopathies and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as likely benign. |