ClinVar Miner

Submissions for variant NM_152618.3(BBS12):c.1893_1894del (p.Pro632fs)

dbSNP: rs1560708847
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 8
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Blueprint Genetics RCV001074774 SCV001240369 pathogenic Retinal dystrophy 2019-06-20 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001238322 SCV001411126 pathogenic Bardet-Biedl syndrome 2023-12-06 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Pro632Phefs*7) in the BBS12 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 79 amino acid(s) of the BBS12 protein. This variant is present in population databases (no rsID available, gnomAD 0.0009%). This premature translational stop signal has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 17160889, 20472660). This variant is also known as 1890delCT. ClinVar contains an entry for this variant (Variation ID: 866623). This variant disrupts a region of the BBS12 protein in which other variant(s) (p.Arg675*) have been determined to be pathogenic (PMID: 20827784, 21642631). 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.
Molecular Biology Laboratory, Fundació Puigvert RCV001281169 SCV001424981 pathogenic Bardet-Biedl syndrome 12 2020-02-01 criteria provided, single submitter research
Laboratory of Medical Genetics (UMR_S 1112), INSERM/Strasbourg University RCV001281169 SCV002559830 pathogenic Bardet-Biedl syndrome 12 2022-08-09 criteria provided, single submitter clinical testing
Fulgent Genetics, Fulgent Genetics RCV001281169 SCV002813959 likely pathogenic Bardet-Biedl syndrome 12 2022-04-20 criteria provided, single submitter clinical testing
Broad Center for Mendelian Genomics, Broad Institute of MIT and Harvard RCV001281169 SCV003922204 likely pathogenic Bardet-Biedl syndrome 12 2023-05-02 criteria provided, single submitter curation The heterozygous p.Pro632PhefsTer7 variant in BBS12 was identified by our study, in the compound heterozygous state with a variant of uncertain significance (ClinVar Variation ID: 444641), in one individual with cone-rod dystrophy. This individual also carried a variant of uncertain significance (ClinVar Variation ID: 444641), however the phase of these variants are unknown at this time. The p.Pro632PhefsTer7 variant in BBS12 has been previously reported in 5 unrelated individuals with Bardet-Biedl syndrome 12 (PMID: 30614526, PMID: 33532864, PMID: 20472660, PMID: 17160889) but has been identified in 0.0009% (1/113452) of European (non-Finnish) chromosomes by the Genome Aggregation Database (gnomAD, http://gnomad.broadinstitute.org; dbSNP rs765915863). Although this variant has been seen in the general population in a heterozygous state, its frequency is low enough to be consistent with a recessive carrier frequency. Of these 5 previously reported unrelated individuals (PMID: 30614526, PMID: 33532864, PMID: 20472660, PMID: 17160889), one was a compound heterozygote who carried a likely pathogenic variant in trans (PMID: 30614526, ClinVar Variation ID: 1151) and four were compound heterozygotes who carried variants of uncertain significance in trans (PMID: 33532864, PMID: 20472660, ClinVar Variation ID: ClinVar ID 974416; PMID: 17160889, NC_000004.12:g.122743410_122743412del, NC_000004.12:g.122743671_122743672insA), which increases the likelihood that the p.Pro632PhefsTer7 variant is pathogenic. This variant has also been reported in ClinVar (Variation ID: 866623) and has been interpreted as pathogenic or likely pathogenic by multiple submitters. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 632 and leads to a premature termination codon 7 amino acids downstream. This termination codon occurs within the last exon and is more likely to escape nonsense mediated decay (NMD) and result in a truncated protein. Loss of function of the BBS12 gene is an established disease mechanism in autosomal recessive Bardet-Biedl syndrome 12. In summary, although additional studies are required to fully establish its clinical significance, this variant is likely pathogenic for autosomal recessive Bardet-Biedl syndrome 12. ACMG/AMP Criteria applied: PVS1_Moderate, PM2_Supporting, PM3_Strong (Richards 2015).
Baylor Genetics RCV001281169 SCV004213976 pathogenic Bardet-Biedl syndrome 12 2022-02-10 criteria provided, single submitter clinical testing
PreventionGenetics, part of Exact Sciences RCV003918665 SCV004730880 pathogenic BBS12-related disorder 2024-01-31 no assertion criteria provided clinical testing The BBS12 c.1893_1894delTC variant is predicted to result in a frameshift and premature protein termination (p.Pro632Phefs*7). This variant has been reported in the compound heterozygous state in patients with Bardet-Biedl syndrome (referred to as c.1890delCT in Stoetzel et al. 2007. PubMed ID: 17160889; Billingsley et al. 2010. PubMed ID: 20472660; Deveault et al. 2011. PubMed ID: 21344540). This variant is reported in 0.00088% of alleles in individuals of European (Non-Finnish) descent in gnomAD. Frameshift variants in BBS12 are expected to be pathogenic. This variant is interpreted as pathogenic.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.