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

dbSNP: rs80359133

Total submissions: 12

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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000045624	SCV000073637	pathogenic	Hereditary breast ovarian cancer syndrome	2024-03-01	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 disrupt the consensus 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.
All of Us Research Program, National Institutes of Health	RCV000083149	SCV004846067	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2023-03-17	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.
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