Total submissions: 8
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000113444 | SCV000300891 | 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. |
Consortium of Investigators of Modifiers of BRCA1/2 |
RCV000113444 | SCV000327231 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2015-10-02 | criteria provided, single submitter | clinical testing | |
Laboratory for Molecular Medicine, |
RCV000496399 | SCV001365928 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-02-08 | criteria provided, single submitter | clinical testing | The p.Glu1857X variant in BRCA2 has been previously reported in at least 4 individuals with BRCA2-associated cancers (Breast Information Core Database (BIC): https://research.nhgri.nih.gov/bic/) and was absent from large population studies. This nonsense variant leads to a premature termination codon at position 1857 which is predicted to lead to a truncated or absent protein. Heterozygous loss of function of the BRCA2 gene is an established disease mechanism in individuals with hereditary breast and ovarian cancer (HBOC). Moreover, this variant was classified as pathogenic on September 8, 2016 by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000300891.2). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon the predicted impact to the protein, absence from the general population and presence in multiple affected individuals. ACMG/AMP Criteria applied: PVS1, PM2, PS4_supporting. |
Labcorp Genetics |
RCV000496399 | SCV001590568 | pathogenic | Hereditary breast ovarian cancer syndrome | 2023-07-17 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu1857*) 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). This variant is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with personal and/or family history of breast and/or ovarian cancer (PMID: 10995809, 29446198). This variant is also known as 5797G>T. ClinVar contains an entry for this variant (Variation ID: 51880). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV002345335 | SCV002650897 | pathogenic | Hereditary cancer-predisposing syndrome | 2022-03-23 | criteria provided, single submitter | clinical testing | The p.E1857* pathogenic mutation (also known as c.5569G>T), located in coding exon 10 of the BRCA2 gene, results from a G to T substitution at nucleotide position 5569. This changes the amino acid from a glutamic acid to a stop codon within coding exon 10. This alteration was observed in 2 of 1035 consecutive, newly diagnosed breast cancer patients with a family history of breast and/or ovarian cancer within a Finnish cohort (Syrjäkoski K et al. J Natl Cancer Inst, 2000 Sep;92:1529-31). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
CHEO Genetics Diagnostic Laboratory, |
RCV003492357 | SCV004240328 | pathogenic | Breast and/or ovarian cancer | 2023-04-24 | criteria provided, single submitter | clinical testing | |
Breast Cancer Information Core |
RCV000113444 | SCV000146634 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2000-06-12 | no assertion criteria provided | clinical testing | |
Research Molecular Genetics Laboratory, |
RCV000496399 | SCV000587773 | pathogenic | Hereditary breast ovarian cancer syndrome | 2014-01-31 | no assertion criteria provided | research |