Total submissions: 4
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, |
RCV001250528 | SCV001425335 | pathogenic | Bardet-Biedl syndrome 5 | 2020-01-18 | criteria provided, single submitter | clinical testing | |
Gene |
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, |
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. |