Total submissions: 18
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000031300 | SCV000244416 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-08-10 | reviewed by expert panel | curation | IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.0000000919 |
Labcorp Genetics |
RCV001086443 | SCV000071718 | benign | Hereditary breast ovarian cancer syndrome | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000759571 | SCV000210695 | benign | not provided | 2019-10-24 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 25637381, 21120943, 26420498, 10755399, 18403564, 22505045, 24323938, 21520273, 20104584, 12955716, 11979449, 25682074, 25348012, 17924331, 21990134, 29988080, 32123317) |
Ambry Genetics | RCV000163020 | SCV000213508 | 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. |
Vantari Genetics | RCV000163020 | SCV000267028 | likely benign | Hereditary cancer-predisposing syndrome | 2016-02-04 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000043705 | SCV000538477 | likely benign | not specified | 2016-03-28 | 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: ExAC: 5/11516 Latino; ClinVar: 4 B/LB, 1 VUS |
Color Diagnostics, |
RCV000163020 | SCV000683390 | likely benign | Hereditary cancer-predisposing syndrome | 2015-06-08 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000043705 | SCV000694490 | benign | not specified | 2020-09-28 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.10045A>G (p.Thr3349Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant allele was found at a frequency of 0.00012 in 251290 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome (0.00012 vs 0.00075), allowing no conclusion about variant significance. c.10045A>G has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer without strong evidence of causality. One patient with the variant showed retention of the wild-type allele and loss of the allele harbouring the variant, suggesting the variant is not deleterious (Osorio_2002). Multifactorial models that incorporate family history, co-segregation, co-occurrence, and tumor pathology has predicted the variant to be likely neutral (Easton_2007, Lindor_2012). Multiple publications report experimental evidence evaluating an impact on protein function: splicing is not affected (Houdayer_2012) and HDR and cell survival assays show no difference from WT controls (Mesman_2018), altogether suggesting the variant has no effect on protein function. Seven clinical diagnostic laboratories and one expert panel (ENIGMA) have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All submitters classified the variant as benign (n=3)/likely benign (n=5). Several submitters cite overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as benign. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000759571 | SCV000888967 | benign | not provided | 2023-05-05 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000031300 | SCV001139283 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000163020 | SCV002533184 | likely benign | Hereditary cancer-predisposing syndrome | 2021-02-03 | criteria provided, single submitter | curation | |
All of Us Research Program, |
RCV000031300 | SCV004846256 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-12-01 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000043705 | SCV005090080 | benign | not specified | 2024-07-31 | criteria provided, single submitter | clinical testing | |
Sharing Clinical Reports Project |
RCV000031300 | SCV000053905 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2008-01-08 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031300 | SCV000145744 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
CSER _CC_NCGL, |
RCV000148421 | SCV000190120 | likely benign | Breast neoplasm | 2014-06-01 | no assertion criteria provided | research | |
Clinical Genetics Laboratory, |
RCV000043705 | SCV001905898 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000043705 | SCV001958277 | benign | not specified | no assertion criteria provided | clinical testing |