Total submissions: 23
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000031788 | SCV001161623 | benign | Breast-ovarian cancer, familial 2 | 2019-06-18 | 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 = 1.80E-06 |
Invitae | RCV000045695 | SCV000073708 | benign | Hereditary breast and ovarian cancer syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000131061 | SCV000185991 | benign | Hereditary cancer-predisposing syndrome | 2014-11-19 | criteria provided, single submitter | clinical testing | Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene |
CHEO Genetics Diagnostic Laboratory, |
RCV000768639 | SCV000219417 | likely benign | Breast and/or ovarian cancer | 2017-08-31 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000031788 | SCV000220479 | likely benign | Breast-ovarian cancer, familial 2 | 2014-07-03 | criteria provided, single submitter | literature only | |
Illumina Clinical Services Laboratory, |
RCV000347597 | SCV000383799 | likely benign | Fanconi anemia, complementation group D1 | 2017-04-28 | criteria provided, single submitter | clinical testing | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Illumina Clinical Services Laboratory, |
RCV000045695 | SCV000383800 | likely benign | Hereditary breast and ovarian cancer syndrome | 2016-06-14 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000454455 | SCV000538499 | uncertain significance | not specified | 2016-06-23 | 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: ClinVar: 8 B/LB |
Department of Pathology and Laboratory Medicine, |
RCV000454455 | SCV000592250 | benign | not specified | 2013-10-25 | criteria provided, single submitter | clinical testing | |
Center for Pediatric Genomic Medicine, |
RCV000034471 | SCV000609923 | likely benign | not provided | 2017-06-20 | criteria provided, single submitter | clinical testing | |
Color Health, |
RCV000131061 | SCV000684018 | likely benign | Hereditary cancer-predisposing syndrome | 2015-03-09 | criteria provided, single submitter | clinical testing | |
Genome Diagnostics Laboratory, |
RCV000031788 | SCV000743357 | benign | Breast-ovarian cancer, familial 2 | 2014-10-09 | criteria provided, single submitter | clinical testing | |
DNA and Cytogenetics Diagnostics Unit, |
RCV000031788 | SCV000744553 | benign | Breast-ovarian cancer, familial 2 | 2017-05-31 | criteria provided, single submitter | clinical testing | |
Institute for Biomarker Research, |
RCV000131061 | SCV000803164 | likely benign | Hereditary cancer-predisposing syndrome | 2018-05-23 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000454455 | SCV000805791 | benign | not specified | 2017-11-20 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000034471 | SCV000883501 | likely benign | not provided | 2018-02-02 | criteria provided, single submitter | clinical testing | The BRCA2 c.9038C>T; p.Thr3013Ile variant (rs28897755) has been reported in the literature in individuals with a personal or family history of hereditary breast and ovarian cancer (Houdayer 2012, Malone 2000, Sanz 2010). However, this variant has also been found incidentally in an individual with no personal or family history of cancer (Johnston 2012). This variant is reported with conflicting interpretations of pathogenicity in ClinVar, with most sources classifying as benign or likely benign (Variation ID: 38205) and is seen in the general population at an overall frequency of 0.02% (65/276280 alleles, including 1 homozygote) in the Genome Aggregation Database. The threonine at codon 3013 is moderately conserved but computational algorithms (SIFT, PolyPhen2, MutationTaster) predict this variant to have no impact on protein function. In agreement with this, functional analysis of this variant protein shows no defects in DNA double-strand break repair using a cell-based homology directed repair assay (Guidugli 2013). Based on the above information, this variant is considered likely benign. REFERENCES Guidugli L et al. A classification model for BRCA2 DNA binding domain missense variants based on homology directed repair activity. Cancer Res. 2013 Jan 1; 73(1): 265–275. Houdayer C et al. Guidelines for splicing analysis in molecular diagnosis derived from a set of 327 combined in silico/in vitro studies on BRCA1 and BRCA2 variants. Hum Mutat. 2012 Aug;33(8):1228-38. Johnston J et al. Secondary Variants in Individuals Undergoing Exome Sequencing: Screening of 572 Individuals Identifies High-Penetrance Mutations in Cancer-Susceptibility Genes. Am J Hum Genet. 2012 Jul 13; 91(1): 97–108. Malone K et al. Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases. Cancer. 2000 Mar 15;88(6):1393-402. Sanz D et al. A high proportion of DNA variants of BRCA1 and BRCA2 is associated with aberrant splicing in breast/ovarian cancer patients. Clin Cancer Res. 2010 Mar 15;16(6):1957-67. |
Mendelics | RCV000031788 | SCV001139243 | likely benign | Breast-ovarian cancer, familial 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000034471 | SCV001249498 | likely benign | not provided | 2019-11-01 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034471 | SCV000043237 | probably not pathogenic | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Likely benign. |
Sharing Clinical Reports Project |
RCV000031788 | SCV000054396 | benign | Breast-ovarian cancer, familial 2 | 2006-03-15 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031788 | SCV000147519 | benign | Breast-ovarian cancer, familial 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
CSER _CC_NCGL, |
RCV000148415 | SCV000190114 | likely benign | Breast neoplasm | 2014-06-01 | no assertion criteria provided | research | |
True Health Diagnostics | RCV000131061 | SCV000787959 | likely benign | Hereditary cancer-predisposing syndrome | 2017-09-07 | no assertion criteria provided | clinical testing |