Total submissions: 22
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001086347 | SCV000072172 | benign | Hereditary breast ovarian cancer syndrome | 2024-01-27 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000129258 | SCV000184018 | likely benign | Hereditary cancer-predisposing syndrome | 2018-10-31 | criteria provided, single submitter | clinical testing | This alteration is classified as likely 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. |
Gene |
RCV000585942 | SCV000210587 | likely benign | not provided | 2018-05-17 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 27376475, 28651617, 26517685, 23525077, 20858050, 30151275) |
Counsyl | RCV000031410 | SCV000488689 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2016-05-26 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000044159 | SCV000694684 | benign | not specified | 2021-03-28 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.3262C>T (p.Pro1088Ser) 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 4.3e-05 in 233286 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome (4.3e-05 vs 0.00075), allowing no conclusion about variant significance. c.3262C>T has been reported in the literature as a reportedly somatic occurrence in non-MSI positive samples from patients with esophageal adenocarcinoma (example, Dulac_2013) and in the MSI instable FFPE specimen derived from a patient with hereditary endometrial carcinoma in whom a germline pathogenic variant in the MSH6 gene had been identified (Jori_2015, patient 5, MSI unstable, MSH6 variant c.3729_3732dupATTA). The variant has also been reported as a germline mutation in the literature in patients with breast/ovarian cancer and head and neck squamous cell carcinoma (HNSCC), without strong evidence for causality (example, Coulet_2010, Buzolin_2017, Schenkel_2016, Chandrasekharappa_2017). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Multiple co-occurrences with other pathogenic variant(s) have been reported in the BIC database (2 - BRCA1 exon13ins6kb, 1 - BRCA1 c.3549_3550delinsT (p.K1183fsX), and 1 - BRCA1 c.4357+1G>A), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Ten clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (benign/likely benign, n=8, VUS, n=2). Taken together, based on at-least 5 reports of the occurrence of this variant in patients with an alternative molecular basis of disease attributed to mutations in MSH6 (n=1) or BRCA1 (n=4) genes and the majority concordance among peers supporting a neutral outcome as outlined above, the variant was classified as benign. |
Genome Diagnostics Laboratory, |
RCV000031410 | SCV000743282 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-06-15 | criteria provided, single submitter | clinical testing | |
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000031410 | SCV000744436 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-09-21 | criteria provided, single submitter | clinical testing | |
Prevention |
RCV000585942 | SCV000805688 | uncertain significance | not provided | 2018-01-10 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000129258 | SCV000902754 | benign | Hereditary cancer-predisposing syndrome | 2016-06-22 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000585942 | SCV001470413 | likely benign | not provided | 2022-09-06 | criteria provided, single submitter | clinical testing | |
Ce |
RCV000585942 | SCV002497654 | uncertain significance | not provided | 2022-02-01 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000129258 | SCV002533777 | likely benign | Hereditary cancer-predisposing syndrome | 2022-01-10 | criteria provided, single submitter | curation | |
University of Washington Department of Laboratory Medicine, |
RCV000129258 | SCV003851815 | 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). |
German Consortium for Hereditary Breast and Ovarian Cancer, |
RCV001086347 | SCV004228270 | likely benign | Hereditary breast ovarian cancer syndrome | 2023-12-19 | criteria provided, single submitter | curation | BRCA2 "coldspot" variant. According to the ClinGen ENIGMA BRCA2 v1.0.0 criteria we chose these criteria: BP1 (strong benign): missense outside a (potentially) clinically important functional domain AND no splicing predicted (SpliceAI ≤0.1), BS1 (supporting benign): FAF > 0.00002 |
ARUP Laboratories, |
RCV000585942 | SCV004563258 | likely benign | not provided | 2023-03-02 | criteria provided, single submitter | clinical testing | |
Sharing Clinical Reports Project |
RCV000031410 | SCV000054015 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2008-10-01 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000031410 | SCV000146198 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Mayo Clinic Laboratories, |
RCV000585942 | SCV000778661 | likely benign | not provided | 2017-07-27 | no assertion criteria provided | clinical testing | |
Diagnostic Laboratory, |
RCV000585942 | SCV001743080 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics Laboratory, |
RCV000585942 | SCV001905951 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000585942 | SCV001960092 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Laboratory of Diagnostic Genome Analysis, |
RCV000585942 | SCV002036082 | likely benign | not provided | no assertion criteria provided | clinical testing |