Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000735935 | SCV001516281 | uncertain significance | Bardet-Biedl syndrome | 2022-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 352 of the BBS12 protein (p.Gln352Pro). This variant is present in population databases (rs767068756, gnomAD 0.04%). This missense change has been observed in individual(s) with clinical features of Bardet-Biedl syndrome (PMID: 30614526). ClinVar contains an entry for this variant (Variation ID: 560429). Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C15"). In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV001375584 | SCV001572481 | uncertain significance | not specified | 2021-04-12 | criteria provided, single submitter | clinical testing | Variant summary: BBS12 c.1055A>C (p.Gln352Pro) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 4.8e-05 in 251302 control chromosomes, predominantly at a frequency of 0.00039 within the South Asian subpopulation in the gnomAD database. This frequency is somewhat lower than the maximum expected for a pathogenic variant in BBS12 causing Bardet-Biedl Syndrome (0.00076), allowing no conclusion about variant significance. The variant, c.1055A>C, has been reported in the literature in at least two apparently homozygous individuals with clinical features of Bardet-Biedl syndrome (Haer-Wigman_2017, Mary_2019). These data indicate that the variant maybe associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Three other submitters have provided clinical-significance assessments for this variant in ClinVar after 2014 without evidence for independent evaluation, and classified the variant as pathogenic (n=1) or VUS (n=2). Based on the evidence outlined above, the variant was classified as VUS-possibly pathogenic. |
| Baylor Genetics | RCV000678525 | SCV004211665 | likely pathogenic | Bardet-Biedl syndrome 12 | 2023-09-23 | criteria provided, single submitter | clinical testing | |
| Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000678525 | SCV000804598 | uncertain significance | Bardet-Biedl syndrome 12 | 2016-09-01 | no assertion criteria provided | clinical testing | |
| Laboratory of Medical Genetics |
RCV000735935 | SCV000839572 | pathogenic | Bardet-Biedl syndrome | 2018-09-15 | no assertion criteria provided | provider interpretation |