Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| SN ONGC Dept of Genetics and Molecular biology Vision Research Foundation | RCV000058870 | SCV000090390 | likely pathogenic | Bardet-Biedl syndrome | 2023-01-02 | criteria provided, single submitter | research | |
| Invitae | RCV000058870 | SCV002267791 | likely pathogenic | Bardet-Biedl syndrome | 2023-07-03 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 138 of the BBS5 protein (p.Arg138His). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. This variant disrupts the p.Arg138 amino acid residue in BBS5. Other variant(s) that disrupt this residue have been observed in individuals with BBS5-related conditions (PMID: 28041643), which suggests that this may be a clinically significant amino acid residue. 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 BBS5 protein function. ClinVar contains an entry for this variant (Variation ID: 68066). This missense change has been observed in individual(s) with clinical features of Bardet-Biedl syndrome or nonsyndromic retinitis pigmentosa (PMID: 22773737, 24400638; Invitae). This variant is present in population databases (rs179363897, gnomAD 0.007%). |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000058870 | SCV004241007 | likely pathogenic | Bardet-Biedl syndrome | 2023-12-12 | criteria provided, single submitter | clinical testing | Variant summary: BBS5 c.413G>A (p.Arg138His) results in a non-conservative amino acid change in the encoded protein sequence. 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 1.2e-05 in 251008 control chromosomes (i.e., 3 heterozygotes, no homozygotes; gnomAD v2.1.1 Exomes dataset). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.413G>A has been reported in the literature in at least two homozygous individuals affected with Bardet-Biedl Syndrome (e.g., Redin_2012, Sathya-Priya_2014, Karam_2023, Gnanasekaran_2023). 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. The following publications have been ascertained in the context of this evaluation (PMID: 37240074, 22773737, 24400638, 30029678, 37431782). Two submitters have reported clinical-significance assessments for this variant to ClinVar after 2014. All submitters classified the variant as likely pathogenic. Based on the evidence outlined above, the variant was classified as likely pathogenic. |