ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3265C>T (p.Gln1089Ter)

dbSNP: rs80358573
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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000113153 SCV000300608 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 (CIMBA), c/o University of Cambridge RCV000113153 SCV000326842 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV000509972 SCV000608125 pathogenic Hereditary cancer-predisposing syndrome 2024-06-17 criteria provided, single submitter clinical testing The p.Q1089* pathogenic mutation (also known as c.3265C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 3265. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This alteration was identified in several studies of families with breast and/or ovarian cancer (Stegel V et al. BMC Med. Genet. 2011 Jan;12:9; 12:9; Cvelbar M et al. Radiol. Oncol., 2017 Jun;51:187-194; Rebbeck TR et al. Hum. Mutat., 2018 05;39:593-620). 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.
Human Genome Sequencing Center Clinical Lab, Baylor College of Medicine RCV000113153 SCV001434848 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2019-02-01 criteria provided, single submitter clinical testing The c.3265C>T (p.Gln1089*) variant in the BRCA2 gene is predicted to introduce a premature translation termination codon. It has been reported in one individual affected with breast cancer (PMID 21232165) and has not been observed in general population databases. Therefore, this c.3265C>T (p.Gln1089*) variant in the BRCA2 gene is classified as pathogenic.
Department of Molecular Diagnostics, Institute of Oncology Ljubljana RCV001310144 SCV001499722 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2020-04-02 criteria provided, single submitter clinical testing
Labcorp Genetics (formerly Invitae), Labcorp RCV001852931 SCV002238468 pathogenic Hereditary breast ovarian cancer syndrome 2024-07-17 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Gln1089*) 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 hereditary breast and ovarian cancer (PMID: 21232165, 29446198). This variant is also known as 3493C>T. ClinVar contains an entry for this variant (Variation ID: 51438). For these reasons, this variant has been classified as Pathogenic.
Baylor Genetics RCV003473328 SCV004211815 pathogenic Familial cancer of breast 2023-11-30 criteria provided, single submitter clinical testing
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet RCV000113153 SCV005046018 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2024-05-27 criteria provided, single submitter clinical testing PVS1; PM2_supporting; PM5_PTC_Strong
Juno Genomics, Hangzhou Juno Genomics, Inc RCV004795968 SCV005415868 pathogenic Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Familial prostate cancer criteria provided, single submitter clinical testing PM2_Supporting+PVS1+PS4_Supporting
Breast Cancer Information Core (BIC) (BRCA2) RCV000113153 SCV000146202 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2002-06-20 no assertion criteria provided clinical testing

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