Total submissions: 12
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000044218 | SCV000072231 | likely benign | Hereditary breast ovarian cancer syndrome | 2024-01-24 | criteria provided, single submitter | clinical testing | |
| Gene |
RCV000587352 | SCV000210235 | likely benign | not provided | 2019-09-04 | criteria provided, single submitter | clinical testing | This variant is associated with the following publications: (PMID: 12670525, 10923033, 11948123) |
| Ambry Genetics | RCV000164685 | SCV000215352 | likely benign | Hereditary cancer-predisposing syndrome | 2019-02-08 | 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 | RCV000587352 | SCV000600555 | uncertain significance | not provided | 2021-04-15 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV000200972 | SCV000694702 | uncertain significance | not specified | 2023-04-01 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.353G>A (p.Arg118His) 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 3.2e-05 in 251012 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. c.353G>A has been reported in the literature as a VUS in cohorts of individuals affected with breast/ovarian cancer as well as in settings of esophageal squamous carcinoma (example, Hu_2002, Machakova_2019, Nguyen-Dumont_2020, Santonocito_2020, Ko_2020). In at-least one of these reports, a patient with esophageal squamous carcinoma also harbored a 12bp deletion at codon 174 of the TP53 gene, although the germline or somatic context of this observation was not clearly specified (example, Hu_2002). A loss of the wild-type BRCA2 allele was observed in this patient. These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine 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=5). Some submitters cite limited overlapping evidence utilized in the context of this evaluation. One submitter reports an unspecified co-occurence with a mutation in same gene (phase unknown), supporting a benign outcome. Based on the evidence outlined above, the variant was classified as uncertain significance. |
| Color Diagnostics, |
RCV000164685 | SCV000903091 | likely benign | Hereditary cancer-predisposing syndrome | 2017-05-09 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV000587352 | SCV001138954 | uncertain significance | not provided | 2022-12-13 | criteria provided, single submitter | clinical testing | |
| Center for Genomic Medicine, |
RCV000200972 | SCV002550247 | uncertain significance | not specified | 2024-02-06 | criteria provided, single submitter | clinical testing | |
| MGZ Medical Genetics Center | RCV003607204 | SCV002579674 | likely benign | Familial cancer of breast | 2024-02-09 | criteria provided, single submitter | clinical testing | ACMG codes applied following ENIGMA VCEP rules: BP1_STR |
| Sharing Clinical Reports Project |
RCV000031426 | SCV000054031 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 2008-02-11 | no assertion criteria provided | clinical testing | |
| Breast Cancer Information Core |
RCV000031426 | SCV000146639 | uncertain significance | Breast-ovarian cancer, familial, susceptibility to, 2 | 1999-01-15 | no assertion criteria provided | clinical testing | |
| 3DMed Clinical Laboratory Inc | RCV000677866 | SCV000804027 | uncertain significance | Cancer of the pancreas | 2018-05-21 | no assertion criteria provided | clinical testing |