Total submissions: 17
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000494843 | SCV000579007 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2017-06-29 | reviewed by expert panel | curation | Synonymous substitution variant, with low bioinformatic likelihood to result in a splicing aberration (Splicing prior probability 0.02; http://priors.hci.utah.edu/PRIORS/). |
Labcorp Genetics |
RCV001082574 | SCV000073389 | likely benign | Hereditary breast ovarian cancer syndrome | 2025-02-01 | criteria provided, single submitter | clinical testing | |
Gene |
RCV000589588 | SCV000210455 | uncertain significance | not provided | 2017-11-09 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.7992T>A at the DNA level. Using alternate nomenclature, this variant would be defined as BRCA2 8220T>A. Although the variant is silent at the coding level, preserving an Isoleucine at codon 2664, it has been demonstrated to cause abnormal splicing. However, the splicing error has been characterized as having a partial, or leaky, effect, with some full length transcript also being produced (Th?ry 2011, Houdayer 2012). BRCA2 c.7992T>A has been reported in a patient with bilateral breast cancer and a family history of early onset breast cancer (Th?ry 2011). BRCA2 c.7992T>A was not observed at a significant allele frequency in large population cohorts (Lek 2016). The nucleotide which is altered, a thymine (T) at base 7992, is conserved among mammals. Based on currently available information, it is unclear whether BRCA2 c.7992T>A is pathogenic or benign. We consider it to be a variant of uncertain significance. |
Ambry Genetics | RCV000163206 | SCV000213729 | likely benign | Hereditary cancer-predisposing syndrome | 2018-08-15 | 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. |
Women's Health and Genetics/Laboratory Corporation of America, |
RCV000045376 | SCV000695118 | uncertain significance | not specified | 2019-09-12 | criteria provided, single submitter | clinical testing | Variant summary: BRCA2 c.7992T>A alters a non-conserved nucleotide resulting in a synonymous change. 5/5 computational tools via ALAMUT predict no significant impact on normal splicing. Another in-silico tool for assessing the pathogenicity of synonymous variants, namely TraP (Transcript-inferred Pathogenicity, Gelfman_2017) predicts that this variant is Benign. However, splicing functional assays demonstrated the variant increases skipping of exon 18 (Thery_2011, Houdayer_2012, Fraile-Bethencourt_2017), however It is complex to interpret the role of variants with partial splicing anomalies in HBOC under the clinical perspective. The variant allele was found at a frequency of 3.2e-05 in 250460 control chromosomes (gnomAD). The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. The variant, c.7992T>A, has been reported in the literature in one individual affected with breast cancer (Thery_BRCA2_EJHG_2011). The data does not allow any conclusion about variant significance. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation (VUS, n=2, likely benign, n=2) and one expert panel (ENIGMA) classified this variant as likely benign. Based on the evidence outlined above, the variant was classified as VUS-possibly benign |
Color Diagnostics, |
RCV000163206 | SCV000910870 | likely benign | Hereditary cancer-predisposing syndrome | 2015-12-04 | criteria provided, single submitter | clinical testing | |
Mendelics | RCV000494843 | SCV001139201 | benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2019-05-28 | criteria provided, single submitter | clinical testing | |
Center for Genomic Medicine, |
RCV000045376 | SCV002551724 | likely benign | not specified | 2025-03-04 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000589588 | SCV002774116 | likely benign | not provided | 2021-08-17 | criteria provided, single submitter | clinical testing | |
Mayo Clinic Laboratories, |
RCV000589588 | SCV004226425 | uncertain significance | not provided | 2022-03-07 | criteria provided, single submitter | clinical testing | BP6, BP7, PS3_supporting |
Department of Pathology and Laboratory Medicine, |
RCV001353768 | SCV000592167 | uncertain significance | Malignant tumor of breast | no assertion criteria provided | clinical testing | The p.Ile2664Ile has been identified in UMD (6X) and the BIC (1X) databases. It is listed in dbSNP database coming from a “clinical source” (ID#: rs80359800) with a “global minor allele frequency of less than 0.001 (1000 genomes). This variant is not expected to have clinical significance because it does not alter an amino acid residue, however it has been suggested to induce incomplete skipping of exon 18 of BRCA2 detected by minigene and in vivo assays (Thery 2011); yet in–silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) predicts no change in the splice site prediction score. In summary, the clinical significance of this variant cannot be determined with certainty at this time. Therefore this variant is a variant of unknown significance (VUS). | |
Foulkes Cancer Genetics LDI, |
RCV000735606 | SCV000863744 | uncertain significance | Breast and/or ovarian cancer | 2015-08-07 | no assertion criteria provided | clinical testing | |
King Laboratory, |
RCV001171450 | SCV001251361 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2; Hereditary breast ovarian cancer syndrome | 2019-09-01 | no assertion criteria provided | research | |
Joint Genome Diagnostic Labs from Nijmegen and Maastricht, |
RCV000589588 | SCV001955500 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
Clinical Genetics DNA and cytogenetics Diagnostics Lab, |
RCV000589588 | SCV001971515 | likely benign | not provided | no assertion criteria provided | clinical testing | ||
BRCAlab, |
RCV000494843 | SCV004243795 | likely benign | Breast-ovarian cancer, familial, susceptibility to, 2 | 2020-03-02 | no assertion criteria provided | clinical testing | |
Prevention |
RCV004542705 | SCV004762829 | likely benign | BRCA2-related disorder | 2020-12-27 | no assertion criteria provided | clinical testing | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). |