ClinVar Miner

Submissions for variant NM_152384.3(BBS5):c.265C>T (p.Arg89Ter)

gnomAD frequency: 0.00001  dbSNP: rs772757329
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 4
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000638356 SCV000759853 pathogenic Bardet-Biedl syndrome 2023-11-27 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg89*) in the BBS5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BBS5 are known to be pathogenic (PMID: 15137946, 16877420, 26325687, 27708425, 28041643, 29806606). This variant is present in population databases (rs772757329, gnomAD 0.003%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 26325687). ClinVar contains an entry for this variant (Variation ID: 531823). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.
Johns Hopkins Genomics, Johns Hopkins University RCV001250528 SCV001425335 pathogenic Bardet-Biedl syndrome 5 2020-01-18 criteria provided, single submitter clinical testing
GeneDx RCV001548296 SCV001768180 pathogenic not provided 2021-11-30 criteria provided, single submitter clinical testing Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 26325687)
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000638356 SCV003844733 pathogenic Bardet-Biedl syndrome 2023-02-14 criteria provided, single submitter clinical testing Variant summary: BBS5 c.265C>T (p.Arg89X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been associated with Bardet-Biedl Syndrome in HGMD. The variant allele was found at a frequency of 1.2e-05 in 250976 control chromosomes. c.265C>T has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (Hirano_2015). These data indicate that the variant may be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three ClinVar submitters have submitted clinical-significance assessments for this variant to ClinVar after 2014. All laboratories classified the variant as pathogenic (n=3). Based on the evidence outlined above, the variant was classified as pathogenic.

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.