Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| ARUP Laboratories, |
RCV000507971 | SCV000602624 | uncertain significance | not specified | 2017-02-24 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000579814 | SCV000682614 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-06-06 | criteria provided, single submitter | clinical testing | This missense variant replaces histidine with tyrosine at codon 84 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 6/245358 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 | RCV000705761 | SCV000834774 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-11-24 | criteria provided, single submitter | clinical testing | This sequence change replaces histidine, which is basic and polar, with tyrosine, which is neutral and polar, at codon 84 of the BAP1 protein (p.His84Tyr). This variant is present in population databases (no rsID available, gnomAD 0.005%). 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: 439431). 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%. 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 | RCV000579814 | SCV001176639 | uncertain significance | Hereditary cancer-predisposing syndrome | 2022-03-01 | criteria provided, single submitter | clinical testing | The p.H84Y variant (also known as c.250C>T), located in coding exon 4 of the BAP1 gene, results from a C to T substitution at nucleotide position 250. The histidine at codon 84 is replaced by tyrosine, an amino acid with similar 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. |
| Laboratorio de Genetica e Diagnostico Molecular, |
RCV000705761 | SCV002512456 | uncertain significance | BAP1-related tumor predisposition syndrome | 2021-04-13 | criteria provided, single submitter | clinical testing | ACMG classification criteria: PM2 |
| Gene |
RCV003318585 | SCV004023114 | uncertain significance | not provided | 2023-01-30 | 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 |
| Baylor Genetics | RCV000705761 | SCV004213229 | uncertain significance | BAP1-related tumor predisposition syndrome | 2023-08-14 | criteria provided, single submitter | clinical testing |