ClinVar Miner

Submissions for variant NM_004656.4(BAP1):c.787A>C (p.Ile263Leu)

dbSNP: rs370841382
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color Diagnostics, LLC DBA Color Health RCV001184272 SCV001350219 uncertain significance Hereditary cancer-predisposing syndrome 2020-02-13 criteria provided, single submitter clinical testing This missense variant replaces isoleucine with leucine at codon 263 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. 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 not been identified 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 (formerly Invitae), Labcorp RCV001351691 SCV001546185 uncertain significance BAP1-related tumor predisposition syndrome 2025-01-28 criteria provided, single submitter clinical testing This sequence change replaces isoleucine, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 263 of the BAP1 protein (p.Ile263Leu). 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: 923506). 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 RCV001184272 SCV002678164 uncertain significance Hereditary cancer-predisposing syndrome 2024-12-07 criteria provided, single submitter clinical testing The p.I263L variant (also known as c.787A>C), located in coding exon 10 of the BAP1 gene, results from an A to C substitution at nucleotide position 787. The isoleucine at codon 263 is replaced by leucine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
GeneDx RCV003322861 SCV004028103 uncertain significance not provided 2023-08-20 criteria provided, single submitter clinical testing Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant does not alter protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

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