ClinVar Miner

Submissions for variant NM_024685.4(BBS10):c.1677C>A (p.Tyr559Ter)

dbSNP: rs375413604
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Total submissions: 11
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000818478 SCV000959093 pathogenic Bardet-Biedl syndrome 2024-01-25 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Tyr559*) in the BBS10 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 165 amino acid(s) of the BBS10 protein. This variant is present in population databases (rs375413604, gnomAD 0.009%). This premature translational stop signal has been observed in individuals with Bardet-Biedl syndrome (PMID: 20472660, 27788217, 28808579). ClinVar contains an entry for this variant (Variation ID: 417949). This variant disrupts a region of the BBS10 protein in which other variant(s) (p.Val707*) have been determined to be pathogenic (PMID: 20472660, 22773737, 25982971, 27486776). 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.
Blueprint Genetics RCV001075280 SCV001240896 pathogenic Retinal dystrophy 2017-09-27 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000818478 SCV001338546 pathogenic Bardet-Biedl syndrome 2020-04-24 criteria provided, single submitter clinical testing Variant summary: BBS10 c.1677C>A (p.Tyr559X) 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 allele was found at a frequency of 4e-05 in 251128 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BBS10 causing Bardet-Biedl Syndrome (4e-05 vs 0.0014). c.1677C>A has been reported in the literature in individuals affected with Bardet-Biedl Syndrome (Billingsley_2010, Feuillan_2011, Knopp_2015, Ohto_2017, Wang_2016). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic/likely pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
GeneDx RCV001528233 SCV001823891 pathogenic not provided 2019-06-04 criteria provided, single submitter clinical testing Nonsense variant in the C-terminus predicted to result in protein truncation, as the last 165 amino acids are lost, and other loss-of-function variants have been reported downstream in the Human Gene Mutation Database (Stenson et al., 2014); Reported as pathogenic in ClinVar but additional evidence is not available (ClinVar SCV000916670.1; Landrum et al., 2016); This variant is associated with the following publications: (PMID: 30029678, 28808579, 27788217, 26003401, 21642631, 20472660, 25366773)
Revvity Omics, Revvity Omics RCV000477827 SCV002017349 pathogenic Bardet-Biedl syndrome 10 2021-10-01 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV000477827 SCV002811652 pathogenic Bardet-Biedl syndrome 10 2022-02-02 criteria provided, single submitter clinical testing
Baylor Genetics RCV000477827 SCV004217407 pathogenic Bardet-Biedl syndrome 10 2023-10-31 criteria provided, single submitter clinical testing
Division of Human Genetics, Children's Hospital of Philadelphia RCV000477827 SCV000536909 likely pathogenic Bardet-Biedl syndrome 10 2016-08-23 no assertion criteria provided research
Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen RCV001528233 SCV001739619 pathogenic not provided no assertion criteria provided clinical testing
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+ RCV001528233 SCV001951022 pathogenic not provided no assertion criteria provided clinical testing
Natera, Inc. RCV000477827 SCV002091750 pathogenic Bardet-Biedl syndrome 10 2020-08-18 no assertion criteria provided clinical testing

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