Submissions for variant NM_000059.4(BRCA2):c.8848delinsCT (p.Lys2950fs)

dbSNP: rs276174912

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)	RCV000114006	SCV000301315	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000114006	SCV000327977	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000985608	SCV001133949	pathogenic	not provided	2019-02-14	criteria provided, single submitter	clinical testing	The variant results in a shift of the reading frame, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Ambry Genetics	RCV002371866	SCV002683444	pathogenic	Hereditary cancer-predisposing syndrome	2019-07-24	criteria provided, single submitter	clinical testing	The c.8848delAinsCT pathogenic mutation, located in coding exon 21 of the BRCA2 gene, results from the deletion of one nucleotide and insertion of two nucleotides causing a translational frameshift with a predicted alternate stop codon (p.K2950Lfs*7). This mutation has been detected in multiple individuals with Hereditary Breast and Ovarian cancer Syndrome (Lubinski et al., Fam. Cancer 2004 ;3(1):1-10; Rebbeck et al. Hum. Mutat. 2018 05;39(5):593-620). Of note, this alteration is also designated as 9076delAinsCT 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.
Breast Cancer Information Core (BIC) (BRCA2)	RCV000114006	SCV000147470	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2001-02-16	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496775	SCV000587972	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research