Total submissions: 4
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001361808 | SCV001557798 | uncertain significance | Bardet-Biedl syndrome | 2024-10-08 | criteria provided, single submitter | clinical testing | This sequence change replaces valine, which is neutral and non-polar, with methionine, which is neutral and non-polar, at codon 461 of the BBS2 protein (p.Val461Met). This variant is present in population databases (rs377000980, gnomAD 0.01%). This missense change has been observed in individual(s) with Bardet–Biedl syndrome (PMID: 33138063). ClinVar contains an entry for this variant (Variation ID: 1053461). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BBS2 protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
Fulgent Genetics, |
RCV002476650 | SCV002781715 | uncertain significance | Bardet-Biedl syndrome 2; Retinitis pigmentosa 74 | 2024-03-27 | criteria provided, single submitter | clinical testing | |
Natera, |
RCV001831222 | SCV002089277 | uncertain significance | Bardet-Biedl syndrome 2 | 2020-03-11 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004733271 | SCV005355206 | uncertain significance | BBS2-related disorder | 2024-09-12 | no assertion criteria provided | clinical testing | The BBS2 c.1381G>A variant is predicted to result in the amino acid substitution p.Val461Met. This variant has been reported in an individual with suspected Bardet-Biedl syndrome; however, a second possible causative variant was not detected in that individual, and the patient also carried heterozygous variants in BBS8 and BBS10 (Jeziorny et al. 2020. PubMed ID: 33138063). This variant is reported in 0.0096% of alleles in individuals of Ashkenazi Jewish descent in gnomAD. At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. |