Total submissions: 1
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001386722 | SCV001587068 | pathogenic | Bardet-Biedl syndrome | 2020-10-08 | criteria provided, single submitter | clinical testing | This variant disrupts the C-terminus of the BBS2 protein. Other variant(s) that disrupt this region (p.Arg703*) have been determined to be pathogenic (PMID: 21344540, 25999675, Invitae). This suggests that variants that disrupt this region of the protein are likely to be causative of disease. Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with BBS2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in the last intron (intron 16) of the BBS2 gene. While this is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. For these reasons, this variant has been classified as Pathogenic. |