Submissions for variant NM_000059.4(BRCA2):c.5405A>G (p.Gln1802Arg)

dbSNP: rs80358764

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478720	SCV000566440	uncertain significance	not provided	2023-10-20	criteria provided, single submitter	clinical testing	Observed in individuals undergoing multi-gene panel testing; however, no information on clinical history was provided (Li et al., 2020); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 5633A>G; This variant is associated with the following publications: (PMID: 29884841, 32377563, 31131967, 31853058)
Ambry Genetics	RCV000575899	SCV000661328	uncertain significance	Hereditary cancer-predisposing syndrome	2024-03-29	criteria provided, single submitter	clinical testing	The p.Q1802R variant (also known as c.5405A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 5405. The glutamine at codon 1802 is replaced by arginine, an amino acid with highly similar properties. 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.
Color Diagnostics, LLC DBA Color Health	RCV000575899	SCV001344942	uncertain significance	Hereditary cancer-predisposing syndrome	2023-10-05	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 1802 of the BRCA2 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 been reported in a multifactorial analysis with co-occurrence and family history likelihood ratios for pathogenicity of 1.0498 and 1.560, respectively (PMID: 31131967). 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	RCV001349274	SCV001543609	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-07-18	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 1802 of the BRCA2 protein (p.Gln1802Arg). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 51857). 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 BRCA2 protein function with a negative predictive value of 95%. 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.
Sema4, Sema4	RCV000575899	SCV002536133	uncertain significance	Hereditary cancer-predisposing syndrome	2022-01-06	criteria provided, single submitter	curation
University of Washington Department of Laboratory Medicine, University of Washington	RCV000575899	SCV003847221	likely benign	Hereditary cancer-predisposing syndrome	2023-03-23	criteria provided, single submitter	curation	Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673).
All of Us Research Program, National Institutes of Health	RCV000083117	SCV004846573	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2023-12-18	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 1802 of the BRCA2 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 been reported in a multifactorial analysis with co-occurrence and family history likelihood ratios for pathogenicity of 1.0498 and 1.560, respectively (PMID: 31131967). 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.
Sharing Clinical Reports Project (SCRP)	RCV000083117	SCV000115191	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000083117	SCV000146608	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2003-12-23	no assertion criteria provided	clinical testing