Total submissions: 10
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000241371 | SCV000300779 | 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. |
Labcorp Genetics |
RCV000168306 | SCV000218989 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-06-05 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 188309). This premature translational stop signal has been observed in individual(s) with pancreatic cancer and prostate cancer (PMID: 26546047, 27433846). This variant is present in population databases (rs786204209, gnomAD 0.0009%). This sequence change creates a premature translational stop signal (p.Thr1566Aspfs*9) 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). |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000241371 | SCV000327069 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Ambry Genetics | RCV000509735 | SCV000608247 | pathogenic | Hereditary cancer-predisposing syndrome | 2021-07-13 | criteria provided, single submitter | clinical testing | The c.4691dupC pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a duplication of C at nucleotide position 4691, causing a translational frameshift with a predicted alternate stop codon (p.T1566Dfs*9). This alteration was identified in an individuals with prostate and pancreatic cancer (Pritchard CC et al. N Engl J Med, 2016 Aug;375:443-53; Smith AL et al. Cancer Lett. 2016 Jan;370(2):302-12). This alteration was also identified 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. |
Quest Diagnostics Nichols Institute San Juan Capistrano | RCV001283923 | SCV001469427 | pathogenic | not provided | 2020-03-17 | criteria provided, single submitter | clinical testing | The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one patient with expected phenotype for this gene, and found in general population data at a frequency that is consistent with pathogenicity. |
Gene |
RCV001283923 | SCV002546650 | pathogenic | not provided | 2022-07-01 | criteria provided, single submitter | clinical testing | Frameshift 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; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Observed in individuals with prostate cancer (Pritchard et al., 2016; Huang et al., 2018); Not observed at significant frequency in large population cohorts (gnomAD); Also known as 4919dupC; This variant is associated with the following publications: (PMID: 27433846, 30720243, 29625052, 33084842) |
Color Diagnostics, |
RCV000509735 | SCV004362076 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-10-11 | criteria provided, single submitter | clinical testing | This variant inserts 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in individuals affected with pancreatic cancer (PMID: 26546047, 31469826) and prostate cancer (PMID: 27433846). This variant has been identified in 1/251062 chromosomes 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. |
Laboratory for Molecular Medicine, |
RCV000168306 | SCV004847676 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-03-22 | criteria provided, single submitter | clinical testing | The p.Thr1566AspfsX9 variant in BRCA2 has been reported in 2 individuals with BRCA2-associated cancers (1 individual with prostate cancer and 1 individual with pancreatic cancer; Pritchard 2016, Smith 2016). It has also been identified in 1/113,456 European chromosomes by gnomAD (http://gnomad.broadinstitute.org). This variant was classified as Pathogenic on September 8, 2016 by the ClinGen-approved NAME expert panel (Variation ID 188309). It is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1566 and leads to a premature termination codon 9 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Loss of function of the BRCA2 gene is an established disease mechanism in autosomal dominant hereditary breast and ovarian cancer syndrome. In summary, this variant meets criteria to be classified as pathogenic for autosomal dominant hereditary breast and ovarian cancer syndrome. ACMG/AMP Criteria applied: PVS1, PM2, PS4_Supporting. |
Department of Pathology and Laboratory Medicine, |
RCV000241371 | SCV000591922 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | no assertion criteria provided | clinical testing | ||
Foulkes Cancer Genetics LDI, |
RCV000735556 | SCV000863694 | pathogenic | Breast and/or ovarian cancer | 2014-07-11 | no assertion criteria provided | clinical testing |