ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8941G>T (p.Glu2981Ter)

dbSNP: rs139052578
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Total submissions: 5
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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) RCV000257646 SCV000324716 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2016-10-18 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 RCV000257646 SCV000327999 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000496957 SCV001405002 pathogenic Hereditary breast ovarian cancer syndrome 2019-10-30 criteria provided, single submitter clinical testing For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer (PMID: 29088781, 29446198). ClinVar contains an entry for this variant (Variation ID: 267121). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu2981*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics RCV002374441 SCV002683943 pathogenic Hereditary cancer-predisposing syndrome 2020-10-01 criteria provided, single submitter clinical testing The p.E2981* pathogenic mutation (also known as c.8941G>T), located in coding exon 21 of the BRCA2 gene, results from a G to T substitution at nucleotide position 8941. This changes the amino acid from a glutamic acid to a stop codon within coding exon 21. This alteration was identified in an individual diagnosed with breast cancer from Chile (Alvarez C et al. Oncotarget, 2017 Sep;8:74233-74243). 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.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto RCV000496957 SCV000587978 pathogenic Hereditary breast ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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