ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.1528G>T (p.Glu510Ter)

dbSNP: rs80358438
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 9
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) 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.
GeneDx 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, Institute of Oncology Ljubljana RCV001310170 SCV001499765 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2020-04-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp 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 (BIC) (BRCA2) RCV000112930 SCV000145882 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2002-05-29 no assertion criteria provided clinical testing
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research 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, Meizhou People's Hospital RCV001004831 SCV002520936 pathogenic Familial cancer of breast no assertion criteria provided curation

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.