Submissions for variant NM_000059.4(BRCA2):c.8941G>T (p.Glu2981Ter)

dbSNP: rs139052578

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)	RCV000257646	SCV000324716	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	RCV000257646	SCV000327999	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496957	SCV001405002	pathogenic	Hereditary breast ovarian cancer syndrome	2019-10-30	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant has been observed in individual(s) with clinical features of hereditary breast and ovarian cancer (PMID: 29088781, 29446198). ClinVar contains an entry for this variant (Variation ID: 267121). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Glu2981*) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product.
Ambry Genetics	RCV002374441	SCV002683943	pathogenic	Hereditary cancer-predisposing syndrome	2020-10-01	criteria provided, single submitter	clinical testing	The p.E2981* pathogenic mutation (also known as c.8941G>T), located in coding exon 21 of the BRCA2 gene, results from a G to T substitution at nucleotide position 8941. This changes the amino acid from a glutamic acid to a stop codon within coding exon 21. This alteration was identified in an individual diagnosed with breast cancer from Chile (Alvarez C et al. Oncotarget, 2017 Sep;8:74233-74243). This alteration was also 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	RCV000496957	SCV000587978	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research