Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV003493338 | SCV004241729 | pathogenic | Familial dysfibrinogenemia | 2023-12-27 | criteria provided, single submitter | clinical testing | Variant summary: The variant involves the deletion of exons 1-5 in the FGA gene. A presumed nomenclature of c.(?_-56)_(*220_?)del has been designated for the purposes of this classification. This deletion includes the entire coding sequence of the gene, and FGA is a gene for which loss-of-function is an established mechanism of disease. As the exact proximal and distal breakpoints are unknown, it may extend beyond the annotated region of the gene to include other flanking genes. The variant was absent in 21694 control chromosomes (gnomAD Structural Variants dataset). To our knowledge, no occurrence of c.(?_-56)_(*220_?)del in individuals affected with Dysfibrinogenemia, Congenital and no experimental evidence demonstrating its impact on protein function have been reported. Two submitters have reported clinical-significance assessments for large deletion variants (approx. 4.1Mb and 3.6Mb) after 2014, which involve the FGA gene together with the deletion of both upstream and downstream flanking genes. One submitter classified the variant as likely pathogenic, and one submitter classified it as uncertain significance, however without evidence for independent evaluation. Based on the evidence outlined above, the variant was classified as pathogenic. |