ClinVar Miner

Submissions for variant NM_004656.4(BAP1):c.916G>A (p.Glu306Lys)

gnomAD frequency: 0.00004  dbSNP: rs779566198
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV000533529 SCV000651905 uncertain significance BAP1-related tumor predisposition syndrome 2024-01-31 criteria provided, single submitter clinical testing This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 306 of the BAP1 protein (p.Glu306Lys). This variant is present in population databases (rs779566198, gnomAD 0.008%). 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: 472717). 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 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 RCV000579725 SCV000682657 uncertain significance Hereditary cancer-predisposing syndrome 2023-07-12 criteria provided, single submitter clinical testing This missense variant replaces glutamic acid with lysine at codon 306 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 performed for this variant. This variant has been reported in an individual affected with BAP1-related disease (PMID: 31323388). This variant has been identified in 5/282544 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 RCV000579725 SCV001180236 uncertain significance Hereditary cancer-predisposing syndrome 2022-03-21 criteria provided, single submitter clinical testing The p.E306K variant (also known as c.916G>A), located in coding exon 10 of the BAP1 gene, results from a G to A substitution at nucleotide position 916. The glutamic acid at codon 306 is replaced by lysine, an amino acid with similar properties. This alteration was identified in 1/183 unselected patients with BAP1-related disease (Zauderer MG et al. J Thorac Oncol, 2019 11;14:1989-1994).This amino acid position is well 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.
Baylor Genetics RCV000533529 SCV004213175 uncertain significance BAP1-related tumor predisposition syndrome 2023-10-24 criteria provided, single submitter clinical testing

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