Submissions for variant NM_000059.4(BRCA2):c.7805+3A>C

dbSNP: rs81002810

Total submissions: 4

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000113820	SCV000327734	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002408542	SCV002673314	uncertain significance	Hereditary cancer-predisposing syndrome	2020-05-29	criteria provided, single submitter	clinical testing	The c.7805+3A>C intronic variant results from an A to C substitution 3 nucleotides after coding exon 15 in the BRCA2 gene. This nucleotide position is well conserved in available vertebrate species. 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). A minigene assay demonstrated that this alteration results in total or partial skipping of coding exon 15 in over 88% of transcripts (Fraile-Bethencourt E et al. Front Genet, 2018 May;9:188). Using two different splice site prediction tools, this alteration is predicted by BDGP to abolish the native splice donor site, but is not predicted to have a deleterious effect on this splice donor site by ESEfinder; however, direct evidence is unavailable. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113820	SCV000147185	uncertain significance	Breast-ovarian cancer, familial, susceptibility to, 2	2003-12-23	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496579	SCV000587911	uncertain significance	not specified	2014-01-31	no assertion criteria provided	research