Total submissions: 7
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000129723 | SCV000184528 | likely benign | Hereditary cancer-predisposing syndrome | 2018-03-26 | 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. |
| Gene |
RCV000429093 | SCV000528641 | likely benign | not specified | 2016-06-16 | 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 | RCV000114012 | SCV000785865 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-12-27 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000129723 | SCV000906957 | uncertain significance | Hereditary cancer-predisposing syndrome | 2023-06-28 | criteria provided, single submitter | clinical testing | This missense variant replaces aspartic acid with histidine at codon 2965 of the BRCA2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). Functional studies have reported that this variant has no impact on BRCA2 function in a homology-directed repair assay (PMID: 23108138, 29394989, 35736817). Multifactorial analysis has reported co-segregation, co-occurrence and family history likelihood ratios for pathogenicity of 1.00, 1.08 and 1.07, respectively (PMID: 23108138, 31131967). This variant also has been detected in a breast cancer case-control meta-analysis in 1/60463 cases and 1/53461 unaffected individuals (PMID: 33471991; Leiden Open Variation Database DB-ID BRCA2_000381). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance. |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000429093 | SCV001426842 | likely benign | not specified | 2020-07-02 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.8893G>C (p.Asp2965His) results in a non-conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 249982 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. Studies utilizing multifactorial likelihood models to assess the clinical significance of BRCA1/BRCA2 variants predict this variant to be likely non-pathogenic (e.g. Guidugli_2013, Lindor_2012). Experimental evidence evaluating an impact on protein function through utilization of a homologous recombination DNA-repair activity assay demonstrated the variant to be neutral/non-pathogenic (e.g. Guidugli_2013, 2018). Four ClinVar submitters (evaluation after 2014) cite the variant as likely benign (n=3) and as uncertain significance (n=1). Based on the evidence outlined above, the variant was classified as likely benign. |
| Invitae | RCV001481867 | SCV001686224 | likely benign | Hereditary breast ovarian cancer syndrome | 2023-06-23 | criteria provided, single submitter | clinical testing | |
| Breast Cancer Information Core |
RCV000114012 | SCV000147481 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing |