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

dbSNP: rs276174907

Total submissions: 9

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
Labcorp Genetics (formerly Invitae), Labcorp	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