Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001230303 | SCV001402778 | pathogenic | Congenital contractural arachnodactyly | 2020-02-24 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This variant affects cysteine residues located within an epidermal growth factor (EGF)–like domain of the FBN2 protein. Cysteine residues in these domains are involved in the formation of disulfide bridges critical for protein structure and stability (PMID: 3495735, 4750422, 16677079). In addition, missense substitutions within the FBN2 EGF-like domains affecting cysteine residues are overrepresented in patients with congenital contractural arachnodactyly (PMID: 18767143). Experimental studies have shown that this variant disrupts mRNA splicing (PMID: 8900230). Disruption of this splice site has been observed in individual(s) with clinical features of FBN2-related conditions (PMID: 8900230, Invitae). This variant is not present in population databases (ExAC no frequency). This sequence change affects an acceptor splice site in intron 33 of the FBN2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. |