Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV002805536 | SCV003023494 | likely pathogenic | Bardet-Biedl syndrome | 2023-10-13 | criteria provided, single submitter | clinical testing | This sequence change replaces threonine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 27 of the BBS2 protein (p.Thr27Pro). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with BBS2-related conditions (PMID: 31630094, 33777945, 33781268). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 1986519). 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 not expected to disrupt BBS2 protein function. 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. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV002805536 | SCV005184878 | pathogenic | Bardet-Biedl syndrome | 2024-05-10 | criteria provided, single submitter | clinical testing | Variant summary: BBS2 c.79A>C (p.Thr27Pro) results in a non-conservative amino acid change located in the Ciliary BBSome complex subunit 2, N-terminal (IPR029430) of the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant was absent in 248912 control chromosomes. c.79A>C has been reported in the literature in either the presumed compound heterozygous or homozygous state in multiple individuals affected with BBS2-spectrum disease ranging from nonsyndromic retinopathy to classic Bardet-Biedl syndrome (example, Bai_2021, Meng_2021, Xu_2020, Zhong_2023). These data indicate that the variant is very 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: 33781268, 33777945, 31630094, 37031301). ClinVar contains an entry for this variant (Variation ID: 1986519). Based on the evidence outlined above, the variant was classified as pathogenic. |
| Fulgent Genetics, |
RCV005019395 | SCV005646167 | pathogenic | Bardet-Biedl syndrome 2; Retinitis pigmentosa 74 | 2024-05-17 | criteria provided, single submitter | clinical testing |