Total submissions: 9
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Evidence- |
RCV000112930 | SCV000300437 | 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. |
Gene |
RCV000485041 | SCV000568454 | pathogenic | not provided | 2016-11-01 | criteria provided, single submitter | clinical testing | This variant is denoted BRCA2 c.1528G>T at the cDNA level and p.Glu510Ter (E510X) at the protein level. The substitution creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon (GAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant has been reported in patients with breast and/or ovarian cancer (Stegel 2011, Novakovic 2012, Henouda 2016, Schenkel 2016) and is considered pathogenic. |
Department of Molecular Diagnostics, |
RCV001310170 | SCV001499765 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 1 | 2020-04-02 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001382424 | SCV001581188 | pathogenic | Hereditary breast ovarian cancer syndrome | 2019-06-04 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Glu510*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in several individuals affected with breast and/or ovarian cancer (PMID: 21232165, 29785153, 26997744, 27376475). ClinVar contains an entry for this variant (Variation ID: 51139). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic. |
Ambry Genetics | RCV004609300 | SCV005100611 | pathogenic | Hereditary cancer-predisposing syndrome | 2024-03-25 | criteria provided, single submitter | clinical testing | The p.E510* pathogenic mutation (also known as c.1528G>T), located in coding exon 9 of the BRCA2 gene, results from a G to T substitution at nucleotide position 1528. This changes the amino acid from a glutamic acid to a stop codon within coding exon 9. This variant has been reported in multiple individuals with personal and/or family history consistent with hereditary breast and ovarian cancer (HBOC) syndrome (Stegel V et al. BMC Med Genet, 2011 Jan;12:9; Novakovi S et al. Int J Oncol, 2012 Nov;41:1619-27; Schenkel LC et al. J Mol Diagn, 2016 Sep;18:657-667; Henouda S et al. Dis Markers, 2016 Feb;2016:7869095; Goidescu IG et al. Clujul Med, 2018 Apr;91:157-165; Moradian MM et al. Hum Genome Var, 2021 Feb;8:9; Zhang Y et al. BMC Cancer, 2022 Aug;22:842; Vidra R et al. Int J Environ Res Public Health, 2022 Apr;19:). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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. |
Breast Cancer Information Core |
RCV000112930 | SCV000145882 | pathogenic | Breast-ovarian cancer, familial, susceptibility to, 2 | 2002-05-29 | no assertion criteria provided | clinical testing | |
Foulkes Cancer Genetics LDI, |
RCV000735525 | SCV000863663 | pathogenic | Breast and/or ovarian cancer | 2009-11-23 | no assertion criteria provided | clinical testing | |
Center of Medical Genetics and Primary Health Care | RCV001004831 | SCV000987241 | pathogenic | Familial cancer of breast | 2020-04-08 | no assertion criteria provided | research | ACMG Guidelines 2015 criteria The BRCA2 variant p.Gln472Ter is a known pathogenic variant in exon 10 and in a non-functional domain. The substitution creates a nonsense variant, which changes a Glutamic Acid to a premature stop codon (GAA>TAA), and is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay which is an established disease mechanism in hereditary breast and ovarian cancer (PVS1 Pathogenic Very Strong). This variant was observed in a mutation hotspot region of 20 pathogenic variants (source, ClinVar) (PM1 Pathogenic Moderate). This variant is not found in GnomAD exomes neither in GnomAD genomes (PM2 Pathogenic Moderate). 3 pathogenic predictions from DANN, EIGEN and MutationTaster versus 1 benign prediction from FATHMM-MKL support its deleterious effect (PP3 Pathogenic Supporting). The variant has been classified as pathogenic by the ClinGen-approved ENIGMA expert panel (ClinVar SCV000300437.2) (PP5 Pathogenic Supporting). In this study this variant was found in a 55-year-old female with unilateral breast cancer and a family history of cancer. Therefore, this variant was classified as a Pathogenic. |
Center for Precision Medicine, |
RCV001004831 | SCV002520936 | pathogenic | Familial cancer of breast | no assertion criteria provided | curation |