Submissions for variant NM_004656.4(BAP1):c.1740G>C (p.Lys580Asn)

dbSNP: rs1438648758

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV001176146	SCV001340025	uncertain significance	Hereditary cancer-predisposing syndrome	2021-12-28	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with asparagine at codon 580 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 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	RCV001235939	SCV001408648	uncertain significance	BAP1-related tumor predisposition syndrome	2024-10-10	criteria provided, single submitter	clinical testing	This sequence change replaces lysine, which is basic and polar, with asparagine, which is neutral and polar, at codon 580 of the BAP1 protein (p.Lys580Asn). 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: 918492). 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.
Fulgent Genetics, Fulgent Genetics	RCV002483947	SCV002799763	uncertain significance	BAP1-related tumor predisposition syndrome; Kury-Isidor syndrome	2022-04-23	criteria provided, single submitter	clinical testing
GeneDx	RCV003236873	SCV003935610	uncertain significance	not provided	2023-06-12	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
Ambry Genetics	RCV001176146	SCV005095039	uncertain significance	Hereditary cancer-predisposing syndrome	2024-06-13	criteria provided, single submitter	clinical testing	The p.K580N variant (also known as c.1740G>C), located in coding exon 14 of the BAP1 gene, results from a G to C substitution at nucleotide position 1740. The lysine at codon 580 is replaced by asparagine, an amino acid with similar properties. This amino acid position is conserved. In addition, this alteration is predicted to be tolerated by in silico analysis. Based on the available evidence, the clinical significance of this variant remains unclear.