ClinVar Miner

Submissions for variant NM_031885.4(BBS2):c.1895G>C (p.Arg632Pro) (rs138043021)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000380902 SCV000398050 pathogenic BBS2-Related Disorders 2017-04-28 criteria provided, single submitter clinical testing The BBS2 c.1895G>C (p.Arg632Pro) missense variant has been reported in six studies in which it is found in a total of 10 patients with BBS2-related disorders. The p.Arg632Pro variant was identified in a compound heterozygous state in four individuals with Bardet-Biedl syndrome (BBS), three of whom carry a third variant in another BBS-associated gene (Katsanis et al. 2001; Bin et al. 2009; Chen et al. 2011; Deveault et al. 2011). The p.Arg632Pro variant was also identified in patients with retinitis pigmentosa, in a homozygous state in four individuals and in a compound heterozygous state in two individuals (Watson et al. 2014; Shevach et al. 2015). Control data are unavailable for this variant, which is reported at a frequency of 0.00021 in the European (non-Finnish) population of the Exome Aggregation Consortium. Functional studies using translation blocking morpholinos for bbs2 in zebrafish demonstrate that the variant was unable to rescue the phenotype and is therefore considered a null allele (Zaghloul et al. 2010). Based on the collective evidence, the p.Arg632Pro variant is classified as pathogenic for BBS2-related disorders. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Integrated Genetics/Laboratory Corporation of America RCV000589221 SCV000699655 pathogenic Bardet-Biedl syndrome 2016-04-05 criteria provided, single submitter clinical testing Variant summary: The c.1895G>C in BBS2 gene is a missense change that alters a conserved nucleotide and 4/4 in silico tools predict deleterious outcome. The variant was observed in the large and broad cohorts of the ExAC project at an allele frequency of 0.012% exclusively in individuals of European descent (0.02%). This frequency does not exceed the maximal expected allele frequency for a pathogenic variant in BBS2 gene (0.085%). Fedick (2014) reports the carrier frequency of 0.261% (0.0064%) for Jewish population. The variant of interest has been reported in multiple BBS pts in compound heterozygous state (Katsanis, 2001, Bin, 2009, Daniels, 2012, Deveault, 2011, Fedick, 2014, and Shevach, 2014), one patient (compound heterozyote) with IRDs (Consugar, 2015), and in 4 individuals (2 homozygotes and 2 compound heterozygotes) presented with nonsyndromic autosomal recessive RP (Shevach, 2014). In functional studies the variant acted as null allele (Zaghloul, 2010). Taking together, the variant was classified as Pathogenic.
Invitae RCV000589221 SCV001218798 likely pathogenic Bardet-Biedl syndrome 2019-12-31 criteria provided, single submitter clinical testing This sequence change replaces arginine with proline at codon 632 of the BBS2 protein (p.Arg632Pro). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and proline. This variant is present in population databases (rs138043021, ExAC 0.02%). This variant has been observed to segregate with retinitis pigmentosa in families (PMID: 25541840, 25133751). This variant has also been reported in individuals with Bardet-Biedl syndrome (PMID: 22401627, 28559085) and in individuals with rod-cone dystrophy or ciliopathy (PMID: 25412400). ClinVar contains an entry for this variant (Variation ID: 4578). Experimental studies have shown that this missense change, p.Arg632Pro, is a null variant in a functional study using a zebrafish model (PMID: 20498079). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.
Blueprint Genetics RCV001073916 SCV001239481 pathogenic Retinal dystrophy 2018-06-19 criteria provided, single submitter clinical testing
OMIM RCV000004840 SCV000025016 pathogenic Bardet-Biedl syndrome 2 2015-03-01 no assertion criteria provided literature only
OMIM RCV000190986 SCV000245873 pathogenic Retinitis pigmentosa 74 2015-03-01 no assertion criteria provided literature only
Counsyl RCV000004840 SCV001132343 likely pathogenic Bardet-Biedl syndrome 2 2019-03-08 no assertion criteria provided clinical testing
Sharon lab,Hadassah-Hebrew University Medical Center RCV001002874 SCV001160907 pathogenic Retinitis pigmentosa 2019-06-23 no assertion criteria provided research

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.