Total submissions: 39
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000031849 | SCV000244498 | benign | Breast-ovarian cancer, familial 2 | 2016-02-16 | reviewed by expert panel | curation | Case-control and frequency data indicate that K3326X does not confer a high risk of cancer (OR 1.3-1.5, dependent on breast or ovarian cancer subtype). |
Invitae | RCV000045926 | SCV000073939 | benign | Hereditary breast and ovarian cancer syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000031849 | SCV000154053 | benign | Breast-ovarian cancer, familial 2 | 2014-01-02 | criteria provided, single submitter | literature only | |
Ambry Genetics | RCV000128910 | SCV000172777 | benign | Hereditary cancer-predisposing syndrome | 2014-11-19 | criteria provided, single submitter | clinical testing | Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;Co-occurence with mutation in same gene (phase unknown);General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance;Intact protein function observed in appropriate functional assay(s);Other strong data supporting benign classification;Seen in trans with a mutation or in homozygous state in individual without severe disease for that gene |
Michigan Medical Genetics Laboratories, |
RCV000031849 | SCV000196031 | benign | Breast-ovarian cancer, familial 2 | 2014-11-03 | criteria provided, single submitter | clinical testing | |
EGL Genetic Diagnostics, |
RCV000120374 | SCV000202309 | benign | not specified | 2015-10-13 | criteria provided, single submitter | clinical testing | |
CSER _CC_NCGL, |
RCV000045926 | SCV000212199 | benign | Hereditary breast and ovarian cancer syndrome | 2015-03-11 | criteria provided, single submitter | research | |
CHEO Genetics Diagnostic Laboratory, |
RCV000735635 | SCV000219429 | likely benign | Breast and/or ovarian cancer | 2017-12-19 | criteria provided, single submitter | clinical testing | |
Genomic Diagnostic Laboratory, |
RCV000045926 | SCV000257622 | benign | Hereditary breast and ovarian cancer syndrome | 2015-07-09 | criteria provided, single submitter | clinical testing | |
Color Health, |
RCV000128910 | SCV000292115 | benign | Hereditary cancer-predisposing syndrome | 2014-11-19 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000120374 | SCV000301783 | benign | not specified | criteria provided, single submitter | clinical testing | ||
Illumina Clinical Services Laboratory, |
RCV000031849 | SCV000383808 | likely benign | Breast-ovarian cancer, familial 2 | 2018-03-06 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Center for Pediatric Genomic Medicine, |
RCV000034474 | SCV000511377 | benign | not provided | 2016-12-27 | criteria provided, single submitter | clinical testing | |
Fulgent Genetics, |
RCV000031849 | SCV000575759 | benign | Breast-ovarian cancer, familial 2 | 2016-02-22 | criteria provided, single submitter | clinical testing | |
Cancer Genetics and Genomics Laboratory, |
RCV000120374 | SCV000586993 | benign | not specified | 2017-04-18 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Molecular Medicine, |
RCV000120374 | SCV000588130 | benign | not specified | 2017-04-20 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV000120374 | SCV000592309 | likely benign | not specified | 2015-11-30 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV001283531 | SCV000602758 | benign | none provided | 2020-08-07 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000120374 | SCV000693648 | benign | not specified | 2017-11-01 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000034474 | SCV000695284 | benign | not provided | 2016-08-12 | criteria provided, single submitter | clinical testing | Variant summary: The BRCA2 c.9976A>T (p.Lys3326X) variant results in a termination codon at the penultimate exon, predicted to cause a truncation of the last 93 amino acids. This variant is not expected to affect any known domain (InterPro) and no truncations downstream of this position have been reported to be pathogenic in literature and databases. This variant was found in 2327/296226 control chromosomes (including 8 homozygotes) at a frequency of 0.0078555, which is approximately 10 times the estimated maximal expected allele frequency of a pathogenic BRCA2 variant (0.0007503), suggesting this variant is likely a benign polymorphism. In addition, several clinical diagnostic laboratories/reputable databases have classified this variant as benign (14)/likely benign (1). Available family, co-occurrence and functional data also show that it is not a disease causing variant. Despite these, this variant is found at considerably high frequency, especially in patients with breast and/or ovarian cancer, raising a possibilty that it may be a risk variant. Using weighted logistic regression, Meeks et al 2016 analyzed data from the large iCOGS study including 76637 cancer case patients and 83796 control patients to estimate odds ratios (ORw) and 95% confidence intervals (CIs) for K3326X variant carriers in relation to breast, ovarian, and prostate cancer risks, with weights defined as probability of not having a pathogenic BRCA2 variant. Other adjustments in the study were adjustment for attained age, consortium study site, and principal components of population structure. From the study, weighted ORs for invasive breast cancer and ovarian cancers were 1.28 (confidence interval 1.17-1.4; P-value=3.84x10e-3) and 1.26 (confidence interval 1.1-1.43; P-value=3.84x10e-3), respectively. The authors conclude that this study provides evidence that the K3326X variant is associated with risk of developing breast and ovarian cancers independent of other pathogenic variants in BRCA2. Hence this variant is a risk allele which attributes a significant but a low risk in development of breast or ovarian cancer. In addition, other genetic/lifestyle/environmental factors may also be playing a part in elevation of risk. Taken together, this variant is classified as Benign for HBOC. |
Genome Diagnostics Laboratory, |
RCV000031849 | SCV000743529 | benign | Breast-ovarian cancer, familial 2 | 2014-10-09 | criteria provided, single submitter | clinical testing | |
DNA and Cytogenetics Diagnostics Unit, |
RCV000031849 | SCV000744794 | benign | Breast-ovarian cancer, familial 2 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000031849 | SCV001139281 | benign | Breast-ovarian cancer, familial 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000034474 | SCV001149001 | likely benign | not provided | 2018-06-01 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV001112896 | SCV001270610 | likely benign | Fanconi anemia, complementation group D1 | 2018-03-06 | criteria provided, single submitter | clinical testing | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as likely benign is not then subjected to further curation. The score for this variant resulted in a classification of likely benign for this disease. |
Institute of Human Genetics, |
RCV000031849 | SCV001429528 | uncertain significance | Breast-ovarian cancer, familial 2 | 2017-09-21 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000120374 | SCV001469470 | benign | not specified | 2020-05-11 | criteria provided, single submitter | clinical testing | |
Biesecker Lab/Clinical Genomics Section, |
RCV000034474 | SCV000043239 | no known pathogenicity | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Benign. |
Sharing Clinical Reports Project |
RCV000031849 | SCV000054457 | benign | Breast-ovarian cancer, familial 2 | 2012-05-01 | no assertion criteria provided | clinical testing | |
ITMI | RCV000120374 | SCV000084526 | not provided | not specified | 2013-09-19 | no assertion provided | reference population | |
Breast Cancer Information Core |
RCV000031849 | SCV000145737 | benign | Breast-ovarian cancer, familial 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Pathway Genomics | RCV000031849 | SCV000187732 | likely benign | Breast-ovarian cancer, familial 2 | 2014-07-24 | no assertion criteria provided | literature only | |
Gene |
RCV000031849 | SCV000484958 | pathogenic | Breast-ovarian cancer, familial 2 | 2016-12-15 | no assertion criteria provided | literature only | |
Research Molecular Genetics Laboratory, |
RCV000120374 | SCV000588018 | benign | not specified | 2014-01-31 | no assertion criteria provided | research | |
Diagnostic Laboratory, |
RCV000031849 | SCV000733342 | benign | Breast-ovarian cancer, familial 2 | no assertion criteria provided | clinical testing | ||
Mayo Clinic Genetic Testing Laboratories, |
RCV000034474 | SCV000778727 | likely benign | not provided | 2017-02-02 | no assertion criteria provided | clinical testing | |
True Health Diagnostics | RCV000128910 | SCV000787962 | benign | Hereditary cancer-predisposing syndrome | 2018-02-20 | no assertion criteria provided | clinical testing | |
Foulkes Cancer Genetics LDI, |
RCV000735635 | SCV000863773 | likely benign | Breast and/or ovarian cancer | 2013-08-02 | no assertion criteria provided | clinical testing | |
Center of Medical Genetics and Primary Health Care | RCV001004846 | SCV000987251 | benign | Malignant tumor of breast | 2020-04-08 | no assertion criteria provided | research | ACMG Guidelines 2015 criteria |