ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.8394_8396delinsAA (p.Arg2799fs)

dbSNP: rs276174907
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Total submissions: 9
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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) RCV000113924 SCV000301274 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 RCV000497283 SCV000210794 pathogenic not provided 2023-06-13 criteria provided, single submitter clinical testing Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 8622_8624delinsAA; This variant is associated with the following publications: (PMID: 22632462, 22776961, 24156927, 26681312)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000113924 SCV000327886 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2015-10-02 criteria provided, single submitter clinical testing
Invitae RCV000496383 SCV000947115 pathogenic Hereditary breast ovarian cancer syndrome 2023-10-07 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Arg2799Asnfs*22) 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 breast cancer, ovarian cancer, and/or pancreatic cancer (PMID: 22776961, 26681312). This variant is also known as 8622delTAGinsAA and c.8394_8396delTAGinsAA. For these reasons, this variant has been classified as Pathogenic.
Department of Molecular Diagnostics, Institute of Oncology Ljubljana RCV001310181 SCV001499776 pathogenic Breast-ovarian cancer, familial, susceptibility to, 1 2020-04-02 criteria provided, single submitter clinical testing
Ambry Genetics RCV002433534 SCV002679774 pathogenic Hereditary cancer-predisposing syndrome 2017-10-02 criteria provided, single submitter clinical testing The c.8394_8396delTAGinsAA pathogenic mutation, located in coding exon 18 of the BRCA2 gene, results from the deletion of 3 nucleotides and insertion of two nucleotides causing a translational frameshift with a predicted alternate stop codon (p.R2799Nfs*22). This mutation has been reported in a patient diagnosed with ovarian cancer who had a family history consistent with HBOC (Schrader KA, Obstet Gynecol 2012 Aug; 120(2 Pt 1):235-40), in an individual diagnosed with both breast and pancreatic cancer (Susswein LR et al. Genet. Med., 2016 Aug;18:823-32), and in an individual with a personal and/or family history of breast and/or ovarian cancer (Tea MK, Maturitas 2014 Jan; 77(1):68-72). Of note, this mutation is also designated as 8622delTAGinsAA in published literature. 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.
Baylor Genetics RCV003473421 SCV004210377 pathogenic Familial cancer of breast 2023-03-06 criteria provided, single submitter clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000113924 SCV000147353 pathogenic Breast-ovarian cancer, familial, susceptibility to, 2 2002-05-29 no assertion criteria provided clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto RCV000496383 SCV000587953 pathogenic Hereditary breast ovarian cancer syndrome 2014-01-31 no assertion criteria provided research

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