Total submissions: 6
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Color Diagnostics, |
RCV000579894 | SCV000682620 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-03-07 | criteria provided, single submitter | clinical testing | This missense variant replaces arginine with cysteine at codon 114 of the BAP1 protein. Computational prediction is inconclusive regarding the impact of this variant on protein structure and function (internally defined REVEL score threshold 0.5 < inconclusive < 0.7, 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 6/251128 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. |
| Labcorp Genetics |
RCV000698949 | SCV000827640 | uncertain significance | BAP1-related tumor predisposition syndrome | 2024-12-22 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with cysteine, which is neutral and slightly polar, at codon 114 of the BAP1 protein (p.Arg114Cys). This variant is present in population databases (rs761048859, gnomAD 0.01%). 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: 489633). Invitae Evidence Modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) indicates that this missense variant is not expected to disrupt BAP1 protein function with a negative predictive value of 80%. 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. |
| Ambry Genetics | RCV000579894 | SCV001181682 | likely benign | Hereditary cancer-predisposing syndrome | 2022-06-29 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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. |
| Fulgent Genetics, |
RCV002483552 | SCV002792027 | uncertain significance | BAP1-related tumor predisposition syndrome; Kury-Isidor syndrome | 2021-10-27 | criteria provided, single submitter | clinical testing | |
| Baylor Genetics | RCV000698949 | SCV004214881 | uncertain significance | BAP1-related tumor predisposition syndrome | 2024-02-20 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV004721466 | SCV005328191 | uncertain significance | not provided | 2024-02-02 | criteria provided, single submitter | clinical testing | In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge |