Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000077359 | SCV000244460 | benign | Breast-ovarian cancer, familial 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 = 0.00000575 |
Invitae | RCV001081769 | SCV000072756 | benign | Hereditary breast and ovarian cancer syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000168582 | SCV000210619 | likely benign | not specified | 2018-03-13 | criteria provided, single submitter | clinical testing | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. |
Ambry Genetics | RCV000163008 | SCV000213496 | 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. |
Counsyl | RCV000077359 | SCV000220254 | likely benign | Breast-ovarian cancer, familial 2 | 2014-04-17 | criteria provided, single submitter | literature only | |
Prevention |
RCV000168582 | SCV000301766 | likely benign | not specified | criteria provided, single submitter | clinical testing | ||
Department of Pathology and Laboratory Medicine, |
RCV000168582 | SCV000591998 | benign | not specified | 2016-01-06 | criteria provided, single submitter | clinical testing | |
Genetic Services Laboratory, |
RCV000168582 | SCV000593719 | likely benign | not specified | 2016-04-20 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000044743 | SCV000600662 | benign | not provided | 2018-09-04 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000168582 | SCV000694899 | likely benign | not specified | 2019-04-19 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.5752C>T (p.His1918Tyr) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 4.4e-05 in 251154 control chromosomes (gnomAD). This frequency is not higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast and Ovarian Cancer (4.4e-05 vs 0.00075), allowing no conclusion about variant significance. c.5752C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer and also, prostate cancer (Ernst_2018, Lu_2015, Kote-Jarai_2011). These reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. A co-occurrence with a pathogenic variant has been reported (LabCorp; BRCA2 c.5946delT, p.Ser1982fsX22), providing supporting evidence for a benign role. In addition, studies utilizing multifactorial likelihood models to assess the clinical significance of BRCA2 variants predict this variant to be neutral/not pathogenic (Lindor_2012, Easton_2007). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six submitters including one expert panel have provided clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation and all have classified the variant as benign (n=2)/likely benign (n=4). Based on the evidence outlined above, the variant was classified as likely benign until additional clinical and functional data become available. |
Color Health, |
RCV000163008 | SCV000910732 | benign | Hereditary cancer-predisposing syndrome | 2015-12-08 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000168582 | SCV000966583 | uncertain significance | not specified | 2018-05-15 | criteria provided, single submitter | clinical testing | proposed classification - variant undergoing re-assessment, contact laboratory |
Illumina Clinical Services Laboratory, |
RCV000077359 | SCV001267162 | uncertain significance | Breast-ovarian cancer, familial 2 | 2018-01-12 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Illumina Clinical Services Laboratory, |
RCV001110578 | SCV001268030 | uncertain significance | Fanconi anemia, complementation group D1 | 2018-01-12 | 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, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. |
Sharing Clinical Reports Project |
RCV000077359 | SCV000109156 | likely benign | Breast-ovarian cancer, familial 2 | 2011-02-24 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000077359 | SCV000146689 | uncertain significance | Breast-ovarian cancer, familial 2 | 2002-05-29 | no assertion criteria provided | clinical testing |