Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002266177 | SCV002547725 | likely pathogenic | Congenital myasthenic syndrome | 2022-05-26 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the deletion of exon 5 in the DOK7 gene. A presumed nomenclature of c.(532+1_533-1)_(652+1_653-1)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 an in-frame deletion change in the DOK7 gene (with a predicted protein level name of p.Trp178_Asp218delinsTyr), affecting the IRS-like phosphotyrosine binding (PTB) domain (amino acids 105-210; IPR002404), which is a protein interaction domain (InterPro). The variant was absent in 21694 control chromosomes (gnomAD database, Structural Variants dataset). To our knowledge, no occurrence of c.(532+1_533-1)_(652+1_653-1)del in individuals affected with Congenital Myasthenic Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. However, variants within exon 5 that preserve the integrity of the reading frame (p.G180A/V, p.C198S) have been reported in affected individuals (HGMD), indicating the functional importance of this protein region. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014, and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |