Total submissions: 19
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000031646 | SCV000244467 | 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 = 0.0000203 |
Invitae | RCV000203624 | SCV000073052 | benign | Hereditary breast ovarian cancer syndrome | 2024-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001703440 | SCV000210634 | likely benign | not provided | 2019-05-28 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 17924331, 24323938, 21990134, 16683254, 20104584, 23683081, 11336395) |
Ambry Genetics | RCV000163010 | SCV000213498 | 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: 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV000768603 | SCV000324848 | likely benign | Breast and/or ovarian cancer | 2021-08-25 | criteria provided, single submitter | clinical testing | |
Department of Pathology and Laboratory Medicine, |
RCV000045039 | SCV000592072 | benign | not specified | 2016-01-15 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000045039 | SCV000593726 | likely benign | not specified | 2016-12-29 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000031646 | SCV000744499 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000163010 | SCV000910744 | benign | Hereditary cancer-predisposing syndrome | 2016-06-30 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000045039 | SCV000918947 | benign | not specified | 2021-04-05 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.6748A>G (p.Thr2250Ala) results in a non-conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00011 in 251358 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome (0.00011 vs 0.00075), allowing no conclusion about variant significance. c.6748A>G has been reported in the literature (example, Arver_2001, Blay_2013, Borg_2010). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. Multifactorial probability models predict a neutral/benign outcome (example, Lindor_2012, Easton_2007). Multiple co-occurrences with other pathogenic variant(s) have been reported in the BIC and UMD databases as well as at our laboratory (example, BRCA1 c.2035A>T, p.Lys679*; BRCA2 c.771_775delTCAAA, p.Asn257LysfsX17; BRCA2 c.262_263delCT, p.Leu88AlafsX12; BRCA2 c.5351dup, p.Asn1784LysfsX3), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Multiple clinical diagnostic laboratories and an 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 (including the expert panel)/likely benign. Based on the evidence outlined above, the variant was classified as benign. |
Sema4, |
RCV000163010 | SCV002536263 | benign | Hereditary cancer-predisposing syndrome | 2020-10-06 | criteria provided, single submitter | curation | |
Center for Genomic Medicine, |
RCV000045039 | SCV002551391 | benign | not specified | 2023-08-15 | criteria provided, single submitter | clinical testing | |
Sharing Clinical Reports Project |
RCV000031646 | SCV000054253 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2009-10-13 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031646 | SCV000146922 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2004-02-20 | no assertion criteria provided | clinical testing | |
Diagnostic Laboratory, |
RCV000031646 | SCV000733287 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | no assertion criteria provided | clinical testing | ||
True Health Diagnostics | RCV000163010 | SCV000787942 | likely benign | Hereditary cancer-predisposing syndrome | 2017-08-17 | no assertion criteria provided | clinical testing | |
Clinical Genetics Laboratory, |
RCV000045039 | SCV001906211 | benign | not specified | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000045039 | SCV001955261 | benign | not specified | no assertion criteria provided | clinical testing | ||
BRCAlab, |
RCV000031646 | SCV004243734 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2020-03-02 | no assertion criteria provided | clinical testing |