ClinVar Miner

Submissions for variant NM_024649.5(BBS1):c.1514_1515del (p.Leu505fs)

gnomAD frequency: 0.00001  dbSNP: rs775769424
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Total submissions: 7
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Counsyl RCV000410181 SCV000486631 pathogenic Bardet-Biedl syndrome 1 2016-07-08 criteria provided, single submitter clinical testing
Centre for Genomic Medicine, Manchester, Central Manchester University Hospitals RCV000410181 SCV001156385 pathogenic Bardet-Biedl syndrome 1 2019-02-01 criteria provided, single submitter clinical testing
Ocular Genomics Institute, Massachusetts Eye and Ear RCV000410181 SCV001573535 pathogenic Bardet-Biedl syndrome 1 2021-04-08 criteria provided, single submitter research The BBS1 c.1514_1515del variant was identified in an individual with retinitis pigmentosa with a presumed recessive inheritance pattern. Through a review of available evidence we were able to apply the following criteria: PM2, PVS1, PP1. Based on this evidence we have classified this variant as Pathogenic.
Invitae RCV001380944 SCV001579172 pathogenic Bardet-Biedl syndrome 2023-09-18 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Leu505Profs*52) in the BBS1 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 89 amino acid(s) of the BBS1 protein. This variant is present in population databases (rs775769424, gnomAD 0.002%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 12524598). ClinVar contains an entry for this variant (Variation ID: 371133). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the BBS1 protein in which other variant(s) (p.Leu548Trpfs*31) have been determined to be pathogenic (PMID: 12677556, 12837689). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV001380944 SCV002598952 pathogenic Bardet-Biedl syndrome 2022-09-06 criteria provided, single submitter clinical testing Variant summary: BBS1 c.1514_1515delTG (p.Leu505ProfsX52) 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 classified as pathogenic by our laboratory. The variant was absent in 251494 control chromosomes. c.1514_1515delTG has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (Examples: Carrigan_2016, Deveault_2011, Jiman_2020 and Mykytyn_2003 etc.). These data indicate that the variant is likely to be associated with disease. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after and classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
Baylor Genetics RCV000410181 SCV004217396 pathogenic Bardet-Biedl syndrome 1 2023-02-12 criteria provided, single submitter clinical testing
Natera, Inc. RCV000410181 SCV002094771 pathogenic Bardet-Biedl syndrome 1 2020-03-12 no assertion criteria provided clinical testing

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