Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Ambry Genetics | RCV000130425 | SCV000185289 | likely benign | Hereditary cancer-predisposing syndrome | 2018-11-30 | 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 | RCV000197376 | SCV000254229 | likely benign | Hereditary breast ovarian cancer syndrome | 2023-12-31 | criteria provided, single submitter | clinical testing | |
Gene |
RCV001704055 | SCV000518147 | likely benign | not provided | 2021-06-06 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 21952622) |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001704055 | SCV000600886 | uncertain significance | not provided | 2022-06-04 | criteria provided, single submitter | clinical testing | In the published literature, this variant has been reported in individuals with breast cancer (PMID: 35264596 (2022)), ovarian cancer (PMID: 34157791 (2021)), prostate cancer (PMID: 21952622 (2011)), and esophageal squamous cell carcinoma (PMID: 31396961 (2020)). This variant has also been reported in unaffected individuals (PMID: 32467295 (2020), 33471991 (2021), see also LOVD (https://databases.lovd.nl/shared/variants/BRCA2)). The frequency of this variant in the general population, 0.000024 (6/250776 chromosomes (Genome Aggregation Database, http://gnomad.broadinstitute.org)), is uninformative in the assessment of its pathogenicity. Analysis of this variant using bioinformatics tools for the prediction of the effect of amino acid changes on protein structure and function yielded predictions that this variant is benign. Based on the available information, we are unable to determine the clinical significance of this variant. |
Color Diagnostics, |
RCV000130425 | SCV000903016 | likely benign | Hereditary cancer-predisposing syndrome | 2015-12-08 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000989093 | SCV001139282 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-08-22 | criteria provided, single submitter | clinical testing | |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000425781 | SCV001361748 | likely benign | not specified | 2022-04-24 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.9986A>G (p.Asn3329Ser) 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 2.4e-05 in 250776 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. Furthermore, the variant has been observed in at-least one woman in a database of women who are cancer free and older than age 70 (FLOSSIES database). c.9986A>G has been reported in the literature in at-least one individual affected with Prostate cancer (example, Kote-Jarai_2011) and as a VUS in one family undergoing testing for the BRCA1/2 genes (example, Zuntini_2018). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast and Ovarian Cancer. At-least one co-occurrence with another pathogenic variant has been reported at our laboratory (BRCA2 c.1755_1759delGAAAA, p.Lys585fsX3), providing supporting evidence for a benign role. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight 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 (likely benign, n=4; VUS, n=4) some of whom report overlapping evidence utilized in the context of this evaluation. Based on the evidence outlined above, the variant was classified as likely benign. |
ARUP Laboratories, |
RCV001704055 | SCV001477524 | uncertain significance | not provided | 2020-06-08 | criteria provided, single submitter | clinical testing | The BRCA2 c.9986A>G; p.Asn3329Ser variant (rs76635144) is reported in the literature in a family affected with breast or ovarian cancer, but without clear evidence for disease association (Zuntini 2018). This variant is reported in ClinVar (Variation ID: 141780), and is only observed on six alleles in the Genome Aggregation Database, indicating it is not a common polymorphism. The asparagine at codon 3329 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.Asn3329Ser variant is uncertain at this time. References: Zuntini R et al. Dealing With BRCA1/2 Unclassified Variants in a Cancer Genetics Clinic: Does Cosegregation Analysis Help?. Front Genet. 2018;9:378. |
Sema4, |
RCV000130425 | SCV002532076 | uncertain significance | Hereditary cancer-predisposing syndrome | 2021-09-18 | criteria provided, single submitter | curation | |
Department of Medical and Surgical Sciences, |
RCV000989093 | SCV004228308 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-09-01 | no assertion criteria provided | clinical testing | BP1(Strong) according to ACMG/AMP classification guidelines specified for BRCA1 & BRCA2 (Classification Criteria V1.0.0 2023-09-08 - https://cspec.genome.network/cspec/ui/svi/affiliation/50087) (PMID: 38160042) |