Total submissions: 14
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000045821 | SCV000073834 | benign | Hereditary breast and ovarian cancer syndrome | 2019-12-31 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000130455 | SCV000185320 | benign | Hereditary cancer-predisposing syndrome | 2015-05-08 | 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. |
Gene |
RCV000160200 | SCV000210551 | benign | not specified | 2016-06-21 | 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. |
Counsyl | RCV000112866 | SCV000220522 | likely benign | Breast-ovarian cancer, familial 2 | 2014-07-17 | criteria provided, single submitter | literature only | |
Michigan Medical Genetics Laboratories, |
RCV000112866 | SCV000267741 | likely benign | Breast-ovarian cancer, familial 2 | 2016-04-21 | criteria provided, single submitter | clinical testing | |
Illumina Clinical Services Laboratory, |
RCV000402194 | SCV000383620 | likely benign | Fanconi anemia, complementation group D1 | 2017-04-27 | 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 allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Illumina Clinical Services Laboratory, |
RCV000112866 | SCV000383621 | likely benign | Breast-ovarian cancer, familial 2 | 2019-09-30 | 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. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. |
Department of Pathology and Laboratory Medicine, |
RCV000160200 | SCV000591720 | likely benign | not specified | 2016-08-10 | criteria provided, single submitter | clinical testing | |
Color Health, |
RCV000130455 | SCV000684062 | likely benign | Hereditary cancer-predisposing syndrome | 2015-06-01 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000758976 | SCV000887964 | benign | not provided | 2018-09-18 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV000769684 | SCV000901097 | likely benign | Breast and/or ovarian cancer | 2016-05-18 | criteria provided, single submitter | clinical testing | |
Integrated Genetics/Laboratory Corporation of America | RCV000160200 | SCV000916903 | benign | not specified | 2020-09-25 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.943T>A (p.Cys315Ser) 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 0.0005 in 238344 control chromosomes, predominantly at a frequency of 0.0054 within the East Asian subpopulation in the gnomAD database. The observed variant frequency within East Asian control individuals in the gnomAD database is approximately 7 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRCA2 causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (0.00075), strongly suggesting that the variant is a benign polymorphism found primarily in populations of East Asian origin. c.943T>A has been reported in the literature in sequencing studies of individuals affected with Hereditary Breast and Ovarian Cancer, but it was also present in several healthy controls at the same time (e.g. Ahmad 2012, Haiman 2013, Suter 2004). Moreover, recent case-control studies performed on South-East Asian cohorts indicated that the variant of interest was found with similar frequencies in breast cancer patients and healthy controls (Lai 2017, Yoon 2016). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. Numerous reported co-occurrences with other pathogenic variant(s) have been reported in the BIC and UMD databases (captured verbatim from the database records, BIC - BRCA2 c.5946_5946delT, p.Ser1982Argfs; BRCA1 c.1687C>T, p.Gln563Ter; BRCA1 c.4035_4035delA, p.Glu1345=fs; BRCA1 c.5263_5264insC, p.Ser1755?fs; BRCA1 c.4148C>G, p.Ser1383Ter; UMD - BRCA1 c.3810C>A, p.Cys1270Ter), providing supporting evidence for a benign role. No experimental evidence demonstrating an impact on protein function was ascertained in the context of this classification. Eleven clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as benign (n=4)/likely benign (n=7). Some submitters cite overlapping evidences utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as benign. |
Ce |
RCV000758976 | SCV001148971 | likely benign | not provided | 2018-04-01 | criteria provided, single submitter | clinical testing | |
Breast Cancer Information Core |
RCV000112866 | SCV000145791 | uncertain significance | Breast-ovarian cancer, familial 2 | 2002-05-29 | no assertion criteria provided | clinical testing |