Total submissions: 10
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ambry Genetics | RCV000222134 | SCV000274539 | likely benign | Hereditary cancer-predisposing syndrome | 2018-05-10 | criteria provided, single submitter | clinical testing | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, 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 |
RCV001281723 | SCV000517308 | likely benign | not provided | 2019-10-14 | criteria provided, single submitter | clinical testing | |
| Invitae | RCV000457281 | SCV000549687 | likely benign | Hereditary breast ovarian cancer syndrome | 2023-11-24 | criteria provided, single submitter | clinical testing | |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001281723 | SCV000600641 | likely benign | not provided | 2020-07-20 | criteria provided, single submitter | clinical testing | |
| Counsyl | RCV000031549 | SCV000784866 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-01-18 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000222134 | SCV000911760 | benign | Hereditary cancer-predisposing syndrome | 2017-02-17 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000420987 | SCV001554633 | likely benign | not specified | 2023-05-01 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.5474C>T (p.Ala1825Val) 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 2.9e-05 in 273532 control chromosomes (gnomAD, Momozawa_2018). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. In a large case-control association study the variant was not detected in any of the breast cancer cases but was detected in controls, and was assigned a classification of Benign (Momozawa_2018). Furthermore, a publication involving the ENIGMA network of collaborators (Parsons_2019) assigned a classification of Likely Benign based on likelihood ratios (LRs) for pathogenicity estimated from clinical data of co-occurrence, family history and bioinformatic predictions. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publications have been ascertained in the context of this evaluation (PMID: 30287823, 31112341, 31131967, 30212499). Eight ClinVar submitters have assessed the variant since 2014: one classified the variant as uncertain significance, six as likely benign, and one as benign. Based on the evidence outlined above, the variant was classified as likely benign. |
| ARUP Laboratories, |
RCV001281723 | SCV002048535 | likely benign | not provided | 2021-10-07 | criteria provided, single submitter | clinical testing | |
| University of Washington Department of Laboratory Medicine, |
RCV000222134 | SCV003848840 | likely benign | Hereditary cancer-predisposing syndrome | 2023-03-23 | criteria provided, single submitter | curation | Missense variant in a coldspot region where missense variants are very unlikely to be pathogenic (PMID:31911673). |
| Sharing Clinical Reports Project |
RCV000031549 | SCV000054154 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2012-03-27 | no assertion criteria provided | clinical testing |