Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000457080 | SCV000564029 | likely pathogenic | Congenital contractural arachnodactyly | 2016-09-16 | criteria provided, single submitter | clinical testing | This variant is a gross deletion of the genomic region encompassing exons 35-36 of the FBN2 gene. This leads to an in-frame deletion, preserving the integrity of the reading frame. This variant is not present in population databases (ExAC no frequency) and has not been reported in the literature in individuals with a FBN2-related disease. This variant deletes two exons that contain calcium-binding EGF-like repeated domains. Several other variants that cause the loss of in-frame calcium-binding EGF-like repeated domains have been shown to be pathogenic for congenital contractural arachnodactyly (PMID: 8900230, 9199560, 11754102, 15121784, 17345643), suggesting that having a consistent number of repeats is important for protein function. In summary, this is a novel deletion of calcium-binding EGF-like repeated domains, and variants that lead to loss of these domains have been shown to be deleterious. However, without additional functional and/or genetic data, this variant has been classified as Likely Pathogenic. |