Submissions for variant NM_004656.4(BAP1):c.779A>G (p.Gln260Arg)

gnomAD frequency: 0.00001  dbSNP: rs878854742

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000228599	SCV000288760	uncertain significance	BAP1-related tumor predisposition syndrome	2024-11-12	criteria provided, single submitter	clinical testing	This sequence change replaces glutamine, which is neutral and polar, with arginine, which is basic and polar, at codon 260 of the BAP1 protein (p.Gln260Arg). This variant is present in population databases (no rsID available, gnomAD 0.002%). 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: 240066). 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.
Color Diagnostics, LLC DBA Color Health	RCV001525774	SCV001735959	uncertain significance	Hereditary cancer-predisposing syndrome	2020-07-28	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 260 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 2/251282 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.
Ambry Genetics	RCV001525774	SCV002673286	uncertain significance	Hereditary cancer-predisposing syndrome	2024-10-17	criteria provided, single submitter	clinical testing	The p.Q260R variant (also known as c.779A>G), located in coding exon 9 of the BAP1 gene, results from an A to G substitution at nucleotide position 779. The glutamine at codon 260 is replaced by arginine, an amino acid with highly similar properties. This amino acid position is conserved. 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.
PreventionGenetics, part of Exact Sciences	RCV003401178	SCV004103917	uncertain significance	BAP1-related disorder	2023-10-11	criteria provided, single submitter	clinical testing	The BAP1 c.779A>G variant is predicted to result in the amino acid substitution p.Gln260Arg. To our knowledge, this variant has not been reported in the literature. This variant is reported in 2 of ~251,000 alleles in gnomAD (http://gnomad.broadinstitute.org/variant/3-52440273-T-C). It is interpreted as uncertain significance in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/240066/). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence.
Myriad Genetics, Inc.	RCV000228599	SCV005406312	likely benign	BAP1-related tumor predisposition syndrome	2024-07-15	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant has been observed at a population frequency that is significantly greater than expected given the associated disease prevalence and penetrance.