Submissions for variant NM_000059.4(BRCA2):c.10049A>G (p.Gln3350Arg)

dbSNP: rs1555290029

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000580599	SCV000683391	uncertain significance	Hereditary cancer-predisposing syndrome	2023-05-25	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 3350 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 not been reported in individuals affected with BRCA2-related disorders 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	RCV000793713	SCV000933079	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-02-02	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 3350 of the BRCA2 protein (p.Gln3350Arg). 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: 489739). 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.
Ambry Genetics	RCV000580599	SCV002706539	uncertain significance	Hereditary cancer-predisposing syndrome	2024-10-28	criteria provided, single submitter	clinical testing	The p.Q3350R variant (also known as c.10049A>G), located in coding exon 26 of the BRCA2 gene, results from an A to G substitution at nucleotide position 10049. The glutamine at codon 3350 is replaced by arginine, an amino acid with highly similar 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.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV003994028	SCV004813745	uncertain significance	not specified	2024-02-14	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004001241	SCV004846257	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2023-06-08	criteria provided, single submitter	clinical testing	This missense variant replaces glutamine with arginine at codon 3350 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 not been reported in individuals affected with BRCA2-related disorders 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.