Total submissions: 13
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000131589 | SCV000186601 | likely benign | Hereditary cancer-predisposing syndrome | 2018-10-09 | criteria provided, single submitter | clinical testing | This alteration is classified as likely 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. |
Invitae | RCV001082225 | SCV000253628 | likely benign | Familial cancer of breast; Fanconi anemia complementation group J | 2024-01-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000588637 | SCV000278891 | likely benign | not provided | 2021-06-08 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 26921362, 28382101, 27978560, 23555315, 28767289, 26689913, 27535533) |
Genetic Services Laboratory, |
RCV000220020 | SCV000593769 | likely benign | not specified | 2017-03-30 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000220020 | SCV000699715 | benign | not specified | 2019-10-04 | criteria provided, single submitter | clinical testing | Variant summary: BRIP1 c.317G>A (p.Arg106His) results in a non-conservative amino acid change located in the ATP-binding domain (IPR014013, IPR014001) and the c2 type DEXD box domain (IPR006554) 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 0.00016 in 282850 control chromosomes, predominantly at a frequency of 0.0014 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 22 fold of the estimated maximal expected allele frequency for a pathogenic variant in BRIP1 causing Hereditary Breast and Ovarian Cancer phenotype (6.3e-05). In addition, this variant was found in 9/2559 African American individuals who are cancer free and older than age 70. These data strongly suggest that the variant is a benign polymorphism found primarily in populations of African origin. c.317G>A has been reported in the literature in individuals affected with various tumor phenotypes (Pearlman 2016, Shindo 2017), however in one of these cases a patient with colorectal cancer also carried a known pathogenic APC variant (c.1759del/p.S587Afs*3, Pearlman 2016). Therefore these reports do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six other clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and classified the variant as Benign (1x), Likely benign (4x) or VUS (1x). Based on the evidence outlined above, the variant was classified as benign. |
Counsyl | RCV000663050 | SCV000786100 | uncertain significance | Fanconi anemia complementation group J; Neoplasm of ovary | 2018-02-21 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131589 | SCV000910802 | benign | Hereditary cancer-predisposing syndrome | 2015-09-23 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000588637 | SCV001134024 | likely benign | not provided | 2022-10-04 | criteria provided, single submitter | clinical testing | |
National Health Laboratory Service, |
RCV002225445 | SCV002505051 | benign | Hereditary breast ovarian cancer syndrome | 2022-04-19 | criteria provided, single submitter | clinical testing | |
Sema4, |
RCV000131589 | SCV002533679 | likely benign | Hereditary cancer-predisposing syndrome | 2021-07-29 | criteria provided, single submitter | curation | |
Myriad Genetics, |
RCV003315912 | SCV004019405 | uncertain significance | Familial cancer of breast | 2023-03-01 | criteria provided, single submitter | clinical testing | This variant is classified as a variant of uncertain significance as there is insufficient evidence to determine its impact on protein function and/or cancer risk. |
Institute for Biomarker Research, |
RCV000131589 | SCV004228082 | benign | Hereditary cancer-predisposing syndrome | 2024-01-04 | criteria provided, single submitter | clinical testing | |
CHEO Genetics Diagnostic Laboratory, |
RCV003492626 | SCV004240401 | likely benign | Breast and/or ovarian cancer | 2022-11-15 | criteria provided, single submitter | clinical testing |