Submissions for variant NM_000059.4(BRCA2):c.7663A>G (p.Lys2555Glu)

dbSNP: rs1566242721

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Color Diagnostics, LLC DBA Color Health	RCV000776410	SCV000911891	uncertain significance	Hereditary cancer-predisposing syndrome	2020-01-29	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with glutamic acid at codon 2555 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001216302	SCV001388092	uncertain significance	Hereditary breast ovarian cancer syndrome	2019-05-05	criteria provided, single submitter	clinical testing	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. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Tolerated"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). This variant has not been reported in the literature in individuals with BRCA2-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change replaces lysine with glutamic acid at codon 2555 of the BRCA2 protein (p.Lys2555Glu). The lysine residue is moderately conserved and there is a small physicochemical difference between lysine and glutamic acid.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001800876	SCV002046266	uncertain significance	not provided	2020-10-04	criteria provided, single submitter	clinical testing
All of Us Research Program, National Institutes of Health	RCV004803204	SCV005425759	uncertain significance	BRCA2-related cancer predisposition	2024-02-22	criteria provided, single submitter	clinical testing	This missense variant replaces lysine with glutamic acid at codon 2555 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). Splice site prediction tools suggest that this variant may not impact RNA splicing. To our knowledge, functional studies have not been performed 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.