Submissions for variant NM_004656.4(BAP1):c.262C>G (p.Pro88Ala)

dbSNP: rs1304265975

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001525289	SCV001735347	uncertain significance	Hereditary cancer-predisposing syndrome	2021-01-26	criteria provided, single submitter	clinical testing	This missense variant replaces proline with alanine at codon 88 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 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.
Ambry Genetics	RCV001525289	SCV002744665	uncertain significance	Hereditary cancer-predisposing syndrome	2024-07-09	criteria provided, single submitter	clinical testing	The p.P88A variant (also known as c.262C>G), located in coding exon 5 of the BAP1 gene, results from a C to G substitution at nucleotide position 262. The proline at codon 88 is replaced by alanine, an amino acid with highly similar properties. This amino acid position is highly conserved in available vertebrate species. In addition, the in silico prediction for this alteration is inconclusive. Based on the available evidence, the clinical significance of this variant remains unclear.
Baylor Genetics	RCV004571049	SCV005053290	uncertain significance	BAP1-related tumor predisposition syndrome	2024-01-16	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV004571049	SCV005701735	uncertain significance	BAP1-related tumor predisposition syndrome	2024-10-23	criteria provided, single submitter	clinical testing	This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 88 of the BAP1 protein (p.Pro88Ala). 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: 1171863). 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 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.