Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000581047 | SCV000682576 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-05-05 | criteria provided, single submitter | clinical testing | This missense variant replaces proline with leucine at codon 474 of the BAP1 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 8/251244 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Invitae | RCV000649777 | SCV000771610 | uncertain significance | BAP1-related tumor predisposition syndrome | 2024-01-24 | criteria provided, single submitter | clinical testing | This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 474 of the BAP1 protein (p.Pro474Leu). This variant is present in population databases (rs770422186, gnomAD 0.02%). 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: 489618). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. 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. |
| Mendelics | RCV000649777 | SCV000838037 | uncertain significance | BAP1-related tumor predisposition syndrome | 2018-07-02 | criteria provided, single submitter | clinical testing | |
| Ambry Genetics | RCV000581047 | SCV001171837 | likely benign | Hereditary cancer-predisposing syndrome | 2022-02-01 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |