Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001893429 | SCV002171037 | uncertain significance | Bardet-Biedl syndrome | 2022-09-13 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu432Argfs*37) in the BBS4 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 88 amino acid(s) of the BBS4 protein. This variant is present in population databases (no rsID available, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with BBS4-related conditions. ClinVar contains an entry for this variant (Variation ID: 1397948). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. 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, |
RCV003155438 | SCV003844294 | uncertain significance | not specified | 2023-02-27 | criteria provided, single submitter | clinical testing | Variant summary: BBS4 c.1294delG (p.Glu432ArgfsX37) results in a premature termination codon, predicted to cause a truncation of the encoded protein, removing the last 51 amino acids. Truncations downstream of this position have not been reported with strong evidence of causality in ClinVar and HGMD and their disease association is uncertain. The variant allele was found at a frequency of 8e-06 in 251432 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.1294delG in individuals affected with Bardet-Biedl Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. One clinical diagnostic laboratory has submitted clinical-significance assessments for this variant to ClinVar after 2014 and classified the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |