Total submissions: 16
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000077309 | SCV000244439 | 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 = 0.0000646 |
Invitae | RCV001084719 | SCV000072240 | benign | Hereditary breast and ovarian cancer syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000131681 | SCV000186717 | likely benign | Hereditary cancer-predisposing syndrome | 2018-10-26 | criteria provided, single submitter | clinical testing | Co-occurence with a mutation in another gene that clearly explains a proband's phenotype;In silico models in agreement (benign);Other data supporting benign classification |
CHEO Genetics Diagnostic Laboratory, |
RCV000735541 | SCV000219329 | likely benign | Breast and/or ovarian cancer | 2017-02-07 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000077309 | SCV000487793 | benign | Breast-ovarian cancer, familial 2 | 2015-11-20 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000440462 | SCV000518131 | likely benign | not specified | 2017-08-15 | 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. |
Department of Pathology and Laboratory Medicine, |
RCV000440462 | SCV000591870 | benign | not specified | 2012-09-05 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000440462 | SCV000694707 | benign | not specified | 2020-11-09 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.3581G>A (p.Gly1194Asp) results in a non-conservative amino acid change located in the BRCA2 repeat region of 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 8.7e-05 in 252186 control chromosomes. This frequency is not significantly higher than expected for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome (8.7e-05 vs 0.00075), allowing no conclusion about variant significance. c.3581G>A, has been reported in the literature in individuals affected with Breast and Ovarian Cancer (e.g. Alsop 2012, Musolino 2007), without strong evidence for pathogenicity. The variant was predicted to be neutral with a multifactorial probability model, based on tumor pathology, clinical histories, family studies and co-occurrence with deleterious mutations (Easton 2007). In addition, UMD BRCA2 database classified this variant as 'likely neutral'. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. At-least two co-occurrences with other pathogenic variant(s) have been observed (BRCA2 c.5130_5133delTGTA, p.Y1710* at our laboratory; TP53 c.524G>A , p.R175H in a family with Li-Fraunemi syndrome, Zampiga_2016), providing supporting evidence for a benign role. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (benign, n=3, likely benign, n=5, VUS, n=1). Based on the lack of any actionable evidence supporting a pathogenic outcome as outlined above, the variant was classified as benign. |
Color Health, |
RCV000131681 | SCV000902800 | likely benign | Hereditary cancer-predisposing syndrome | 2015-11-08 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000077309 | SCV001139068 | likely benign | Breast-ovarian cancer, familial 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV001111917 | SCV001269525 | uncertain significance | Fanconi anemia, complementation group D1 | 2019-05-20 | 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 did not allow this variant to be ruled in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Illumina Clinical Services Laboratory, |
RCV000077309 | SCV001269526 | uncertain significance | Breast-ovarian cancer, familial 2 | 2019-05-20 | 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). Publications were found based on this search. However, the evidence from the literature, in combination with allele frequency data from public databases where available, was not sufficient to rule this variant in or out of causing disease. Therefore, this variant is classified as a variant of unknown significance. |
Biesecker Lab/Clinical Genomics Section, |
RCV000034439 | SCV000043207 | variant of unknown significance | not provided | 2012-07-13 | no assertion criteria provided | research | Converted during submission to Uncertain significance. |
Sharing Clinical Reports Project |
RCV000077309 | SCV000109106 | uncertain significance | Breast-ovarian cancer, familial 2 | 2008-05-02 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000077309 | SCV000146262 | uncertain significance | Breast-ovarian cancer, familial 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Foulkes Cancer Genetics LDI, |
RCV000735541 | SCV000863679 | uncertain significance | Breast and/or ovarian cancer | no assertion criteria provided | clinical testing |