Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130258 | SCV000185102 | likely benign | Hereditary cancer-predisposing syndrome | 2024-03-20 | criteria provided, single submitter | clinical testing | This alteration is classified as likely 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. |
Labcorp Genetics |
RCV000205313 | SCV000259920 | uncertain significance | Hereditary breast ovarian cancer syndrome | 2023-09-30 | criteria provided, single submitter | clinical testing | This sequence change replaces arginine, which is basic and polar, with lysine, which is basic and polar, at codon 841 of the BRCA2 protein (p.Arg841Lys). This variant is present in population databases (rs587781915, gnomAD 0.0009%). 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: 141657). 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. 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. |
Counsyl | RCV000663004 | SCV000786009 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2018-01-31 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000130258 | SCV000906043 | uncertain significance | Hereditary cancer-predisposing syndrome | 2019-05-03 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001284076 | SCV001469664 | uncertain significance | not provided | 2020-08-12 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV001532896 | SCV001748686 | uncertain significance | not specified | 2021-07-01 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.2522G>A (p.Arg841Lys) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4e-06 in 248086 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.2522G>A in individuals affected with Hereditary Breast And Ovarian Cancer Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as uncertain significance. Based on the evidence outlined above, the variant was classified as uncertain significance. |
University of Washington Department of Laboratory Medicine, |
RCV000130258 | SCV003848384 | 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). |
Myriad Genetics, |
RCV000663004 | SCV004019716 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-04-03 | criteria provided, single submitter | clinical testing | This variant is considered 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]. This variant has been observed in trans with a known pathogenic variant in one or more individuals lacking clinical features consistent with gene-specific recessive disease. |