Total submissions: 19
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001080657 | SCV000073875 | benign | Hereditary breast ovarian cancer syndrome | 2025-02-03 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000129724 | SCV000184529 | benign | Hereditary cancer-predisposing syndrome | 2014-11-19 | criteria provided, single submitter | clinical testing | This alteration is classified as benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. |
Gene |
RCV000586984 | SCV000210690 | likely benign | not provided | 2021-01-26 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 25637381, 26332594, 24607278, 11139248, 25556971, 21120943, 27153395, 25985138, 27062684, 23704879, 27067391, 30254663, 31131559, 32123317) |
Laboratory for Molecular Medicine, |
RCV000045862 | SCV000538501 | uncertain significance | not specified | 2016-08-11 | criteria provided, single submitter | clinical testing | Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: Reported in 1 male breast cancer patient - multiple other publications report as nonpathogenic; ClinVar: 5 B/LB, 1 VUS |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000586984 | SCV000600869 | likely benign | not provided | 2023-03-09 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000586984 | SCV000695254 | likely benign | not provided | 2017-07-06 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000129724 | SCV000902714 | benign | Hereditary cancer-predisposing syndrome | 2016-07-23 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000586984 | SCV001158350 | likely benign | not provided | 2024-08-05 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000586984 | SCV001502178 | likely benign | not provided | 2025-04-01 | criteria provided, single submitter | clinical testing | BRCA2: BP4, BS1 |
Sema4, |
RCV000129724 | SCV002532052 | likely benign | Hereditary cancer-predisposing syndrome | 2020-10-23 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000045862 | SCV005090077 | likely benign | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing | |
Institute for Biomarker Research, |
RCV001080657 | SCV005688936 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2024-11-20 | criteria provided, single submitter | clinical testing | The missense variant NM_000059.4(BRCA2):c.9586A>G (p.Lys3196Glu) has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The variant is observed in one or more well-documented healthy adults. There is a small physicochemical difference between lysine and glutamic acid, which is not likely to impact secondary protein structure as these residues share similar properties. The gene BRCA2 has a low rate of benign missense variation as indicated by a high missense variants Z-Score of 1.00. The gene BRCA2 contains 148 pathogenic missense variants, indicating that missense variants are a common mechanism of disease in this gene. For these reasons, this variant has been classified as Uncertain Significance. |
Molecular Diagnostics Laboratory, |
RCV000129724 | SCV005901885 | benign | Hereditary cancer-predisposing syndrome | 2025-02-13 | criteria provided, single submitter | clinical testing | BS1, BP1_Strong c.9586A>G, located in exon 26 of the BRCA2 gene, is predicted to result in the substitution of Lys by Glu at codon 3196, p.(Lys3196Glu). This position is outside a (potentially) clinically important functional domain and, moreover, the SpliceAI algorithm predicts no significant impact on splicing (BP1_strong). It was found in 10/34260 alleles, with a filter allele frequency of 0.015% at 95% confidence, within the Latino population in the gnomAD v2.1 (non-cancer, exome only subset) (BS1). To our knowledge, no well-stablished functional studies have been reported for this variant. This variant has been reported in the ClinVar database (6x benign, 8x likely benign,4x uncertain significance), in the LOVD database (1x likely benign, 10x uncertain significance) and in the BRCA Exchange database as Not yet reviewed. Based on currently available information, the variant c.9586A>G should be considered a benign variant. |
Sharing Clinical Reports Project |
RCV000031834 | SCV000054442 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-05-01 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031834 | SCV000147670 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2004-02-20 | no assertion criteria provided | clinical testing | |
CSER _CC_NCGL, |
RCV000148420 | SCV000190119 | likely benign | Breast neoplasm | 2014-06-01 | no assertion criteria provided | research | |
Department of Pathology and Laboratory Medicine, |
RCV001269375 | SCV000592294 | benign | Malignant tumor of breast | no assertion criteria provided | clinical testing | The BRCA2 p.Lys3196Glu variant was identified in 1 of 74 proband chromosomes (frequency: 0.014) from individuals or families with male breast cancer, and was not identified in 200 control chromosomes from healthy individuals (Kwiatkowska 2000); however, an insufficient number of controls were included in these studies to determine the frequency of this variant in the general population. The variant was also identified in dbSNP (ID: rs80359228) “With uncertain significance”, with a minor allele frequency of 0.000/1 (1000 Genomes Project), NHLBI Exome Sequencing Project (Exome Variant Server), HGMD, ClinVar database, the BIC database (8 X with unknown clinical importance), and UMD (7 X as an unknown variant). The variant was classified as a benign variant by the Sharing Clinical Reports Project (SCRP) (submitted within the ClinVar database and derived from Myriad reports). The variant was identified by the Exome Variant Server project in 1 of 8600 European American alleles (frequency: 0.0001), although this low number of observations and low frequency is not substantive enough to determine the prevalence of the variant in the general population and its relationship to disease. The p.Lys3196 residue is not conserved in mammals and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein; this information is not very predictive of pathogenicity. One study (Santos 2014), found the variant co-occurring with a pathogenic BRCA2 variant c.8488-1G>A, increasing the likelihood that the p.Lys3196Glu variant does not have clinical significance. In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign. | |
Foulkes Cancer Genetics LDI, |
RCV000735631 | SCV000863769 | uncertain significance | Breast and/or ovarian cancer | 2003-02-11 | no assertion criteria provided | clinical testing | |
Center of Medical Genetics and Primary Health Care | RCV001269375 | SCV001448723 | benign | Malignant tumor of breast | no assertion criteria provided | clinical testing |