Submissions for variant NM_000059.4(BRCA2):c.9816T>G (p.Asp3272Glu)

dbSNP: rs56111359

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Labcorp Genetics (formerly Invitae), Labcorp	RCV000045900	SCV000073913	uncertain significance	Hereditary breast ovarian cancer syndrome	2024-07-30	criteria provided, single submitter	clinical testing	This sequence change replaces aspartic acid, which is acidic and polar, with glutamic acid, which is acidic and polar, at codon 3272 of the BRCA2 protein (p.Asp3272Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with uterine serous carcinoma (PMID: 22811390). ClinVar contains an entry for this variant (Variation ID: 52902). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985632	SCV001133990	uncertain significance	not provided	2019-05-27	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001019789	SCV001181193	uncertain significance	Hereditary cancer-predisposing syndrome	2023-06-07	criteria provided, single submitter	clinical testing	The p.D3272E variant (also known as c.9816T>G), located in coding exon 26 of the BRCA2 gene, results from a T to G substitution at nucleotide position 9816. The aspartic acid at codon 3272 is replaced by glutamic acid, an amino acid with highly similar properties. This alteration was detected in an individual diagnosed with uterine serous carcinoma (Pennington KP et al. Cancer, 2013 Jan;119:332-8). This amino acid position is highly 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.
Mayo Clinic Laboratories, Mayo Clinic	RCV000985632	SCV004226427	uncertain significance	not provided	2022-08-08	criteria provided, single submitter	clinical testing	BP4, PM2
All of Us Research Program, National Institutes of Health	RCV000112813	SCV004837597	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2023-12-15	criteria provided, single submitter	clinical testing	This missense variant replaces aspartic acid with glutamic acid at codon 3272 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 an individual affected with uterine serous carcinoma (PMID: 22811390) and in a multifactorial analysis with co-occurrence and family history likelihood ratios for pathogenicity of 1.0246 and 1.6256, 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.
Baylor Genetics	RCV004566860	SCV005059046	uncertain significance	Familial cancer of breast	2024-02-18	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000112813	SCV000145715	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing