Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003226658 | SCV003922596 | likely pathogenic | Chronic granulomatous disease | 2023-03-17 | criteria provided, single submitter | clinical testing | Variant summary: The variant identified by MLPA or other technology involves the duplication of exons 2-4 in the NCF1 gene. A presumed nomenclature of c.(72+1_73-1)_(395+1_396-1)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 a frameshift in the NCF1 gene. The variant was absent in 20992 control chromosomes in the gnomAD database (structural variants dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.(72+1_73-1)_(395+1_396-1)dup in individuals affected with Chronic Granulomatous Disease and no experimental evidence demonstrating its impact on protein function have been reported. Duplication of exon 2 has been classifed as pathogenic in ClinVar (ID 870704). No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |