Submissions for variant NM_000059.4(BRCA2):c.8474del (p.Ala2825fs)

dbSNP: rs80359711

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113939	SCV000301280	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.
Ambry Genetics	RCV000166065	SCV000216827	pathogenic	Hereditary cancer-predisposing syndrome	2014-10-17	criteria provided, single submitter	clinical testing	The c.8474delC (also known as 8702delC) pathogenic mutation, located in coding exon 18 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 8474, causing a translational frameshift with a predicted alternate stop codon. This deletion has been reported in a Scandinavian breast cancer family (Hakansson S et al., AJHG 1997, (60):1068). Since frameshifts are typically deleterious in nature, this alteration is interpreted as a disease-causing mutation (ACMG Recommendations for Standards for Interpretation and Reporting of Sequence Variations. Revision 2007. Genet Med. 2008;10:294).
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000113939	SCV000327899	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001383607	SCV001582814	pathogenic	Hereditary breast ovarian cancer syndrome	2020-05-11	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.Ala2825Aspfs*38) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant has been observed in individual(s) with breast and/or ovarian cancer (PMID: 9150154, 26833046, 26360800). This variant is also known as c.8702delC in the literature. ClinVar contains an entry for this variant (Variation ID: 52597). For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584).
Department of Clinical Genetics, Copenhagen University Hospital, Rigshospitalet	RCV000113939	SCV005045918	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2024-05-27	criteria provided, single submitter	clinical testing	PVS1; PM2_supporting; PM5_PTC_Strong
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113939	SCV000147371	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing