Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV001084667 | SCV000072013 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-01-28 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000130196 | SCV000185033 | likely benign | Hereditary cancer-predisposing syndrome | 2018-10-01 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: 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. |
Counsyl | RCV000077279 | SCV000488788 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2016-06-15 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000044000 | SCV000512346 | likely benign | not provided | 2021-02-28 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 21523855, 23929434, 24817641, 27803004, 10923033) |
Color Diagnostics, |
RCV000130196 | SCV000688758 | likely benign | Hereditary cancer-predisposing syndrome | 2017-03-06 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000435008 | SCV001362930 | likely benign | not specified | 2022-10-10 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.2459A>G (p.Asp820Gly) results in a non-conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 1.6e-05 in 242584 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.2459A>G has been reported in the literature in an individual affected with pancreatic ductal adenocarcinoma, however a co-occurring pathogenic variant (PALB2 c.1725dupG, pSer576Glufs*2) have been also found in this patient (Boeck 2017), providing supporting evidence for a benign role. It has also been reported as a VUS in individuals undergoing testing for breast cancer (example, Akter_2019). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Four of these classified the variant as likely benign. Based on the evidence outlined above, no conclusive evidence supporting a pathogenic outcome has been ascertained over a time frame of 5 years since its original classification by our laboratory and all subsequent evidence seem to support a benign outcome. Therefore, the variant was classified as likely benign. |
University of Washington Department of Laboratory Medicine, |
RCV000130196 | SCV003848337 | 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). |
Preventiongenetics, |
RCV003415788 | SCV004108567 | uncertain significance | BRCA2-related condition | 2022-10-27 | criteria provided, single submitter | clinical testing | The BRCA2 c.2459A>G variant is predicted to result in the amino acid substitution p.Asp820Gly. This variant was reported in an individual with pancreatic ductal adenocarcinoma, however a pathogenic PALB2 c.1725dupG (p.Ser576Glufs*2) variant and an uncertain ATM c.1066-6T>G (intronic) variant were also reported in that individual (Boeck et al 2017. PubMed ID: 27803004). This variant is reported in 0.011% of alleles in individuals of South Asian descent in gnomAD (http://gnomad.broadinstitute.org/variant/13-32910951-A-G) and has conflicting interpretations regarding is pathogenicity in ClinVar, ranging from uncertain to likely benign (https://www.ncbi.nlm.nih.gov/clinvar/variation/51291/). While this variant may be benign, at this time, its clinical significance is uncertain due to the absence of conclusive functional and genetic evidence. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000044000 | SCV004219542 | uncertain significance | not provided | 2023-03-08 | criteria provided, single submitter | clinical testing | The frequency of this variant in the general population, 0.00011 (3/28276 chromosomes, http://gnomad.broadinstitute.org), is uninformative in assessment of its pathogenicity. In the published literature, the variant has been reported in individuals with pancreatic cancer (PMID: 27803004 (2017)), renal cell carcinoma (PMID: 29610387 (2018)), and breast cancer (PMID: 31477031 (2019)). In a large-scale breast cancer association study, the variant was observed in individuals with breast cancer as well as in unaffected controls (PMID: 33471991 (2021), see also LOVD (http://databases.lovd.nl/shared/genes/BRCA2)). Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
Sharing Clinical Reports Project |
RCV000077279 | SCV000109076 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2011-04-08 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000077279 | SCV000146052 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2001-02-16 | no assertion criteria provided | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000044000 | SCV001932220 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000044000 | SCV001952525 | likely benign | not provided | no assertion criteria provided | clinical testing |