ClinVar Miner

Submissions for variant NM_024685.4(BBS10):c.145C>T (p.Arg49Trp) (rs768933093)

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Total submissions: 6
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000210662 SCV000262879 pathogenic Inborn genetic diseases 2014-08-22 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: LIKELY POSITIVE: Relevant Alteration(s) Detected
Centre for Mendelian Genomics,University Medical Centre Ljubljana RCV000626963 SCV000747666 pathogenic Retinal dystrophy; Macular degeneration; Postaxial hand polydactyly; Intellectual disability; Foot polydactyly; High-frequency hearing impairment 2017-01-01 criteria provided, single submitter clinical testing
Counsyl RCV000576728 SCV000678121 pathogenic Bardet-Biedl syndrome 10 2017-01-24 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000576728 SCV000893986 pathogenic Bardet-Biedl syndrome 10 2018-10-31 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000576728 SCV000381160 pathogenic Bardet-Biedl syndrome 10 2017-04-28 criteria provided, single submitter clinical testing The BBS10 c.145C>T (p.Arg49Trp) missense variant has been reported in nine studies in which it is found in at least 15 patients with Bardet-Biedl syndrome, including in four in a homozygous state and in 11 in a compound heterozygous state (Stoetzel et al. 2006; Hjortshøj et al. 2010; Muller et al. 2010; Bennouna-Greene et al. 2011; Chen et al. 2011; Imhoff et al. 2011; Schaefer et al. 2011; Lindstrand et al. 2014; Scheidecker et al. 2015). The p.Arg49Trp variant was absent from 192 control chromosomes and is reported at a frequency of 0.00009 in the European (non-Finnish) population of the Exome Aggregation Consortium. Functional studies demonstrated that the p.Arg49Trp variant was a null allele and failed to rescue morphant phenotypes seen in zebrafish embryos in which translation of the BBS10 protein was suppressed (Zaghloul et al. 2010). Based on the collective evidence, the p.Arg49Trp variant is considered to be pathogenic for Bardet-Biedl syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000799037 SCV000938684 pathogenic Bardet-Biedl syndrome 2018-10-05 criteria provided, single submitter clinical testing This sequence change replaces arginine with tryptophan at codon 49 of the BBS10 protein (p.Arg49Trp). The arginine residue is weakly conserved and there is a moderate physicochemical difference between arginine and tryptophan. This variant is present in population databases (rs768933093, ExAC 0.009%). This variant has been observed to be homozygous or in combination with another BBS10 variant in individuals affected with Bardet-Biedl syndrome (PMID: 16582908, 20472660, 22410627, 25982971). ClinVar contains an entry for this variant (Variation ID: 225010). Experimental studies in zebrafish have shown that this missense change abolishes BBS10 protein function (PMID: 20498079). For these reasons, this variant has been classified as Pathogenic.

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