ClinVar Miner

Submissions for variant NM_152618.3(BBS12):c.2023C>T (p.Arg675Ter) (rs752202089)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Clinical Services Laboratory,Illumina RCV000670073 SCV000447429 likely pathogenic Bardet-Biedl syndrome 12 2017-04-28 criteria provided, single submitter clinical testing The BBS12 c.2023C>T (p.Arg675Ter) stop-gained variant has been reported in two studies in a total of three individuals, either with Bardet-Biedl syndrome (BBS) or suspected to have BBS, in a compound heterozygous state (Dulfer et al. 2010; Chen et al. 2011). Of these individuals, two were siblings who also had a heterozygous frameshift variant in the BBS10 gene. In this family, the father was heterozygous for the BBS12 p.Arg675Ter variant and the mother was heterozygous for the other variants. The other individual who had the p.Arg675Ter variant in a compound heterozygous state also had a heterozygous missense variant in the BBS1 gene. The p.Arg675Ter variant was absent from 288 controls but is reported at a frequency of 0.00002 in the European (non-Finnish) population of the Exome Aggregation Consortium, however this is based on one allele in a region of good sequence coverage so the variant is presumed to be rare. Based on the evidence and due to potential impact of stop-gained variants, the p.Arg675Ter variant is classified as likely pathogenic for Bardet-Biedl syndrome. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV000302878 SCV000759859 pathogenic Bardet-Biedl syndrome 2017-09-25 criteria provided, single submitter clinical testing This sequence change results in a premature translational stop signal in the BBS12 gene (p.Arg675*). While this is not anticipated to result in nonsense mediated decay, it is expected to delete the last 36 amino acids of the BBS12 protein. This variant is present in population databases (rs752202089, ExAC 0.002%). This variant has been reported in combination with BBS12 variants in individuals affected with Bardet-Biedl syndrome (PMID: 20827784, 21642631). In one of these individuals, this p.Arg675* variant was observed on the opposite chromosome (in trans) from a pathogenic variant (PMID: 20827784). These findings are consistent with autosomal recessive inheritance, and suggests that this variant contributes to disease. It has also been observed ClinVar contains an entry for this variant (Variation ID: 347505). For these reasons, this variant has been classified as Pathogenic.
Counsyl RCV000670073 SCV000794888 pathogenic Bardet-Biedl syndrome 12 2017-10-18 criteria provided, single submitter clinical testing
Fulgent Genetics,Fulgent Genetics RCV000670073 SCV000894332 pathogenic Bardet-Biedl syndrome 12 2018-10-31 criteria provided, single submitter clinical testing
Laboratory of Medical Genetics, INSERM RCV000302878 SCV000839577 pathogenic Bardet-Biedl syndrome 2018-09-15 no assertion criteria provided provider interpretation

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