Submissions for variant NM_000059.4(BRCA2):c.2660A>G (p.Glu887Gly)

dbSNP: rs587782015

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV000130441	SCV000185305	uncertain significance	Hereditary cancer-predisposing syndrome	2019-09-28	criteria provided, single submitter	clinical testing	The p.E887G variant (also known as c.2660A>G), located in coding exon 10 of the BRCA2 gene, results from an A to G substitution at nucleotide position 2660. The glutamic acid at codon 887 is replaced by glycine, an amino acid with similar properties. This amino acid position is not 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.
GeneDx	RCV000486429	SCV000566116	uncertain significance	not provided	2016-05-09	criteria provided, single submitter	clinical testing	This variant is denoted BRCA2 c.2660A>G at the cDNA level, p.Glu887Gly (E887G) at the protein level, and results in the change of a Glutamic Acid to a Glycine (GAG>GGG). Using alternate nomenclature, this variant would be defined as BRCA2 2888A>G. This variant has not, to our knowledge, been published in the literature as pathogenic or benign. BRCA2 Glu887Gly was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, suggesting it is not a common benign variant in these populations. Since Glutamic Acid and Glycine differ in polarity, charge, size or other properties, this is considered a non-conservative amino acid substitution. BRCA2 Glu887Gly occurs at a position that is not conserved and is not located in a known functional domain. In silico analyses predict that this variant is unlikely to alter protein structure or function. Based on currently available evidence, it is unclear whether BRCA2 Glu887Gly is a pathogenic or benign variant. We consider it to be a variant of uncertain significance.
Color Diagnostics, LLC DBA Color Health	RCV000130441	SCV000683495	uncertain significance	Hereditary cancer-predisposing syndrome	2023-03-01	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glycine at codon 887 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 hereditary cancer in the literature. This variant has been identified in 1/230764 chromosomes 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	RCV000637382	SCV000758838	likely benign	Hereditary breast ovarian cancer syndrome	2024-07-01	criteria provided, single submitter	clinical testing
University of Washington Department of Laboratory Medicine, University of Washington	RCV000130441	SCV003848482	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	RCV004804153	SCV004845041	uncertain significance	BRCA2-related cancer predisposition	2024-07-29	criteria provided, single submitter	clinical testing	This missense variant replaces glutamic acid with glycine at codon 887 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 hereditary cancer in the literature. This variant has been identified in 1/230764 chromosomes 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.
Myriad Genetics, Inc.	RCV003998059	SCV005084464	likely benign	Breast-ovarian cancer, familial, susceptibility to, 2	2024-06-20	criteria provided, single submitter	clinical testing	This variant is considered likely benign. This variant is strongly associated with less severe personal and family histories of cancer, typical for individuals without pathogenic variants in this gene [PMID: 25085752].