Submissions for variant NM_000059.4(BRCA2):c.8276_8279del (p.Val2759fs)

dbSNP: rs886040753

Total submissions: 5

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000257321	SCV000324635	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	RCV000257321	SCV000327847	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496696	SCV002225756	pathogenic	Hereditary breast ovarian cancer syndrome	2021-08-30	criteria provided, single submitter	clinical testing	This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Val2759Alafs*17) 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 has not been reported in the literature in individuals affected with BRCA2-related conditions. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 267063).
Ambry Genetics	RCV002429205	SCV002679165	pathogenic	Hereditary cancer-predisposing syndrome	2019-10-18	criteria provided, single submitter	clinical testing	The c.8276_8279delTGGG pathogenic mutation, located in coding exon 17 of the BRCA2 gene, results from a deletion of 4 nucleotides at nucleotide positions 8276 to 8279, causing a translational frameshift with a predicted alternate stop codon (p.V2759Afs*17). This alteration was 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	RCV000496696	SCV000587943	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research