Submissions for variant NM_000059.4(BRCA2):c.8770G>T (p.Glu2924Ter)

dbSNP: rs80359133

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000083149	SCV000301309	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.
Invitae	RCV000045624	SCV000073637	pathogenic	Hereditary breast ovarian cancer syndrome	2023-10-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu2924*) 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 is not present in population databases (gnomAD no frequency). This premature translational stop signal has been observed in individual(s) with high risk for breast and/or ovarian cancer (PMID: 29446198). ClinVar contains an entry for this variant (Variation ID: 52675). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000083149	SCV000327966	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Department of Pathology and Molecular Medicine, Queen's University	RCV000045624	SCV000588122	pathogenic	Hereditary breast ovarian cancer syndrome	2017-04-20	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000583458	SCV000689155	pathogenic	Hereditary cancer-predisposing syndrome	2020-02-26	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 22 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in an individual who underwent genetic testing (PMID: 28152038). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759680	SCV000889167	pathogenic	not provided	2023-03-24	criteria provided, single submitter	clinical testing	This nonsense variant causes the premature termination of BRCA2 protein synthesis. This variant has not been reported in large, multi-ethnic general populations (http://gnomad.broadinstitute.org). In the published literature, the variant has been reported in a worldwide screening study of families with BRCA1 and BRCA2 mutations (PMID: 29446198 (2018)). The variant has also been reported in an individual undergoing multi-gene panel testing (PMID: 28152038 (2017)). Based on the available information, this variant is classified as pathogenic.
Ambry Genetics	RCV000583458	SCV001179529	pathogenic	Hereditary cancer-predisposing syndrome	2018-06-18	criteria provided, single submitter	clinical testing	The p.E2924* pathogenic mutation (also known as c.8770G>T), located in coding exon 21 of the BRCA2 gene, results from a G to T substitution at nucleotide position 8770. This changes the amino acid from a glutamic acid to a stop codon within coding exon 21. 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.
Sharing Clinical Reports Project (SCRP)	RCV000083149	SCV000115223	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000083149	SCV000147458	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000045624	SCV000587970	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
BRCAlab, Lund University	RCV000083149	SCV004243835	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2020-03-02	no assertion criteria provided	clinical testing