Submissions for variant NM_004656.4(BAP1):c.1651C>G (p.Arg551Gly)

dbSNP: rs755664216

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000553151	SCV000651861	uncertain significance	BAP1-related tumor predisposition syndrome	2024-10-21	criteria provided, single submitter	clinical testing	This sequence change replaces arginine, which is basic and polar, with glycine, which is neutral and non-polar, at codon 551 of the BAP1 protein (p.Arg551Gly). 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: 472675). 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) has been performed for this missense variant. However, the output from this modeling did not meet the statistical confidence thresholds required to predict the impact of this variant on BAP1 protein function. 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.
Mendelics	RCV000553151	SCV000838035	uncertain significance	BAP1-related tumor predisposition syndrome	2018-07-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV001180327	SCV001345230	uncertain significance	Hereditary cancer-predisposing syndrome	2020-03-09	criteria provided, single submitter	clinical testing	This missense variant replaces arginine with glycine at codon 551 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.
Ambry Genetics	RCV001180327	SCV002705560	uncertain significance	Hereditary cancer-predisposing syndrome	2021-03-08	criteria provided, single submitter	clinical testing	The p.R551G variant (also known as c.1651C>G), located in coding exon 13 of the BAP1 gene, results from a C to G substitution at nucleotide position 1651. The arginine at codon 551 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. 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.