Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002532103 | SCV003441838 | pathogenic | Bardet-Biedl syndrome | 2024-05-08 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 315 of the BBS2 protein (p.Arg315Gln). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with Bardet-Biedl syndrome and/or retinitis pigmentosa (PMID: 11567139, 12677556, 33777945, 33921607). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 555022). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt BBS2 protein function with a negative predictive value of 80%. Experimental studies have shown that this missense change affects BBS2 function (PMID: 20498079). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant disrupts the p.Arg315 amino acid residue in BBS2. Other variant(s) that disrupt this residue have been determined to be pathogenic (PMID: 11567139, 27894351). This suggests that this residue is clinically significant, and that variants that disrupt this residue are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. |
Dept Of Ophthalmology, |
RCV003889960 | SCV004705064 | likely pathogenic | Retinal dystrophy | 2023-10-01 | criteria provided, single submitter | research | |
Fulgent Genetics, |
RCV005019139 | SCV005644039 | likely pathogenic | Bardet-Biedl syndrome 2; Retinitis pigmentosa 74 | 2024-06-14 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000670759 | SCV000795655 | uncertain significance | Bardet-Biedl syndrome 2 | 2017-11-15 | flagged submission | clinical testing |