Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV000045861 | SCV000073874 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-01-19 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000129471 | SCV000184241 | likely benign | Hereditary cancer-predisposing syndrome | 2018-09-07 | 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000083162 | SCV000296504 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2016-06-07 | criteria provided, single submitter | clinical testing | |
Counsyl | RCV000083162 | SCV000487986 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-12-10 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001705703 | SCV000532127 | likely benign | not provided | 2019-05-21 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 16905680, 25348012, 26295337, 23704879, 30212499, 28726806) |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000427171 | SCV000695253 | uncertain significance | not specified | 2019-09-07 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.9583A>G (p.Thr3195Ala) 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 1.2e-05 in 251412 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.9583A>G has been reported in the literature in one family with high risk of breast or ovarian cancer (Simard_2007). This report does 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 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=3; uncertain significance, n=3). Based on the evidence outlined above, the variant was classified as uncertain significance. |
Color Diagnostics, |
RCV000129471 | SCV000911111 | benign | Hereditary cancer-predisposing syndrome | 2017-01-09 | criteria provided, single submitter | clinical testing | |
ARUP Laboratories, |
RCV000427171 | SCV001158035 | uncertain significance | not specified | 2018-11-29 | criteria provided, single submitter | clinical testing | The BRCA2 c.9583A>G; p.Thr3195Ala variant (rs80359227), is reported in the literature in at least one individual with a family history of breast and/or ovarian cancer (Simard 2007). This variant is reported as uncertain significance/likely benign by multiple laboratories in ClinVar (Variation ID: 52872), and is only observed on three alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The threonine at codon 3195 is weakly conserved, and computational analyses (SIFT, PolyPhen-2) predict that this variant is tolerated. Due to limited information, the clinical significance of the p.Thr3195Ala variant is uncertain at this time. References: Simard J et al. Evaluation of BRCA1 and BRCA2 mutation prevalence, risk prediction models and a multistep testing approach in French-Canadian families with high risk of breast and ovarian cancer. J Med Genet. 2007 Feb;44(2):107-21. |
Sharing Clinical Reports Project |
RCV000083162 | SCV000115236 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-05-01 | no assertion criteria provided | clinical testing | |
Breast Cancer Information Core |
RCV000083162 | SCV000147669 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2004-02-20 | no assertion criteria provided | clinical testing |