Total submissions: 11
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000031187 | SCV000154009 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2014-01-02 | criteria provided, single submitter | literature only | |
| Gene |
RCV000159889 | SCV000209973 | benign | not specified | 2014-08-20 | 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. |
| Invitae | RCV000456921 | SCV000560246 | likely benign | Hereditary breast ovarian cancer syndrome | 2023-12-06 | criteria provided, single submitter | clinical testing | |
| Color Diagnostics, |
RCV000581092 | SCV000683203 | benign | Hereditary cancer-predisposing syndrome | 2016-12-19 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000159889 | SCV000699163 | likely benign | not specified | 2019-02-08 | criteria provided, single submitter | clinical testing | Variant summary: BRCA1 c.4676-7C>T alters a conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 5/5 computational tools predict no significant impact on normal splicing. This prediction was confirmed by a study that demonstrated by RNA analysis from patient lymphocytes that the variant does not affect splicing (Byers 2016). The variant allele was found at a frequency of 3.6e-05 in 249608 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.4676-7C>T has been reported in the literature in individuals affected with Hereditary Breast and Ovarian Cancer (Judkins 2005, Byers 2016), however without strong evidence for causality. Co-occurrence with another pathogenic variant has also been reported (ATM c.7271T>G, p.Val2424Gly; Byers 2016), providing supporting evidence for a benign role. In addition, multifactorial probability models, performing systematic assessments of variants of unknown significance in the BRCA genes, which included analysis of co-occurrence in trans with known deleterious mutations, personal and family history of cancer, tumor pathology and co-segregation with disease in pedigrees, predicted this variant to be likely neutral (Easton 2007 and Lindor 2012). Two clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation, and both laboratories classified the variant as benign (1x) / likely benign (1x). Our laboratory classified this variant as a "VUS-possibly normal" in October-2016, however, no new evidence supporting pathogenicity have been reported since our original classification. Therefore, the overall evidence seems to be shifting from uncertain significance to likely benign consistent with all the evidence outlined above. Based on this, until more clinical and functional data become available, the variant was classified as likely benign. |
| Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001800319 | SCV002047338 | likely benign | not provided | 2021-05-19 | criteria provided, single submitter | clinical testing | |
| ARUP Laboratories, |
RCV001800319 | SCV002048003 | likely benign | not provided | 2021-09-18 | criteria provided, single submitter | clinical testing | |
| Sema4, |
RCV000581092 | SCV002537768 | likely benign | Hereditary cancer-predisposing syndrome | 2021-09-16 | criteria provided, single submitter | curation | |
| All of Us Research Program, |
RCV000031187 | SCV004818803 | benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2023-03-23 | criteria provided, single submitter | clinical testing | |
| Sharing Clinical Reports Project |
RCV000031187 | SCV000053787 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 1 | 2012-03-22 | no assertion criteria provided | clinical testing | |
| Breast Cancer Information Core |
RCV000031187 | SCV000145155 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 1 | 2000-06-12 | no assertion criteria provided | clinical testing |