Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001175029 | SCV001338547 | likely pathogenic | Bardet-Biedl syndrome | 2020-04-24 | criteria provided, single submitter | clinical testing | Variant summary: BBS10 c.1184A>G (p.His395Arg) results in a non-conservative amino acid change located in the Chaperonin Cpn60/TCP-1 family. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 251242 control chromosomes (gnomAD). c.1184A>G has been reported in the literature in the homozygous state in two siblings affected with classic Bardet-Biedl Syndrome (Chakrabarty_2020). Furthermore, a case study from a university reported the variant in homozygosity in another patient diagnosed with Bardet-Biedl Syndrome (Fracchia_2015). These data indicate that the variant is likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Invitae | RCV001175029 | SCV002277436 | pathogenic | Bardet-Biedl syndrome | 2024-01-25 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with arginine, which is basic and polar, at codon 395 of the BBS10 protein (p.His395Arg). This variant is present in population databases (no rsID available, gnomAD 0.003%). This missense change has been observed in individual(s) with Bardet-Biedl syndrome (PMID: 31639430). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 917794). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt BBS10 protein function with a positive predictive value of 80%. For these reasons, this variant has been classified as Pathogenic. |
| SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation | RCV001175029 | SCV003915906 | pathogenic | Bardet-Biedl syndrome | criteria provided, single submitter | research | This variant was observed in compound heterozygosity with variant NC_000012.11:g.76741536dup | |
| Baylor Genetics | RCV003462643 | SCV004217461 | likely pathogenic | Bardet-Biedl syndrome 10 | 2023-04-11 | criteria provided, single submitter | clinical testing |