Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000797395 | SCV000936949 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces tyrosine, which is neutral and polar, with cysteine, which is neutral and slightly polar, at codon 189 of the BAP1 protein (p.Tyr189Cys). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BAP1-related conditions. ClinVar contains an entry for this variant (Variation ID: 643642). 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 BAP1 protein function with a positive predictive value of 80%. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. 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. |
| Genetic Services Laboratory, |
RCV001816855 | SCV002070811 | uncertain significance | not specified | 2019-06-24 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV002345762 | SCV002652090 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-08-11 | criteria provided, single submitter | clinical testing | The p.Y189C variant (also known as c.566A>G), located in coding exon 7 of the BAP1 gene, results from an A to G substitution at nucleotide position 566. The tyrosine at codon 189 is replaced by cysteine, an amino acid with highly dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |