Total submissions: 11
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000113053 | SCV000300526 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2016-09-08 | reviewed by expert panel | curation | Variant allele predicted to encode a truncated non-functional protein. |
Ambry Genetics | RCV000131057 | SCV000185987 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-11-29 | criteria provided, single submitter | clinical testing | The p.Y839* pathogenic mutation (also known as c.2517C>A), located in coding exon 10 of the BRCA2 gene, results from a C to A substitution at nucleotide position 2517. This changes the amino acid from a tyrosine to a stop codon within coding exon 10. This alteration was identified twice in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). In addition to the clinical data presented in the literature, this alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
Gene |
RCV000223462 | SCV000279394 | pathogenic | not provided | 2022-09-26 | criteria provided, single submitter | clinical testing | Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in several families with Hereditary Breast and Ovarian Cancer syndrome (LaDuca et al., 2017; Rebbeck et al., 2018); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2745C>A; This variant is associated with the following publications: (PMID: 28152038, 29446198, 32295079) |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000113053 | SCV000326719 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Color Diagnostics, |
RCV000131057 | SCV000906892 | pathogenic | Hereditary cancer-predisposing syndrome | 2023-02-20 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been detected in families suspected of having hereditary breast and ovarian cancer (PMID: 28152038, 29446198). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Labcorp Genetics |
RCV001385315 | SCV001585130 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-09-01 | criteria provided, single submitter | clinical testing | This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with increased risk of breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 51299). For these reasons, this variant has been classified as Pathogenic. This sequence change creates a premature translational stop signal (p.Tyr839*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). |
Baylor Genetics | RCV003473316 | SCV004210426 | pathogenic | Familial cancer of breast | 2023-11-14 | criteria provided, single submitter | clinical testing | |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV000223462 | SCV004219546 | pathogenic | not provided | 2023-01-31 | criteria provided, single submitter | clinical testing | This nonsense variant causes the premature termination of BRCA2 protein synthesis. It has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in high-risk breast and ovarian cancer families (PMID: 29446198 (2018)). Based on the available information, this variant is classified as pathogenic. |
All of Us Research Program, |
RCV000113053 | SCV004847064 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2023-12-13 | criteria provided, single submitter | clinical testing | This variant changes 1 nucleotide in exon 11 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been detected in families suspected of having hereditary breast and ovarian cancer (PMID: 28152038, 29446198). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic. |
Breast Cancer Information Core |
RCV000113053 | SCV000146060 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2000-06-12 | no assertion criteria provided | clinical testing | |
CZECANCA consortium | RCV001270986 | SCV001451797 | pathogenic | Breast and/or ovarian cancer | 2019-06-11 | no assertion criteria provided | clinical testing |