Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003994816 | SCV004813227 | pathogenic | Hereditary factor VIII deficiency disease | 2024-02-26 | criteria provided, single submitter | clinical testing | Variant summary: The variant involves the duplication of exon 14 in the F8 gene. It is assumed to be a tandem duplication in direct orientation (PMIDs: 25640679, 30054569). This Copy Number Variant (CNV) is expected to alter the reading frame and predicted to result in a truncation or absence of the encoded protein due to nonsense mediated decay (NMD). A presumed nomenclature of c.(2113+1_2114-1)_(5219+1_5220-1)dup has been designated for the purposes of this classification. The variant was absent in 16120 control chromosomes (gnomAD). c.(2113+1_2114-1)_(5219+1_5220-1)dup has been reported in the literature in individuals affected with Factor VIII Deficiency (Hemophilia A; Rost_2008, Johnsen_2017, Feng_2021). These data indicate that the variant is likely to be associated with disease. The following publications have been ascertained in the context of this evaluation (PMID: 33245802, 18752578, 29296726). No submitters have cited clinical-significance assessments for this variant to ClinVar. Based on the evidence outlined above, the variant was classified as pathogenic. |