Submissions for variant NM_000059.4(BRCA2):c.5344C>T (p.Gln1782Ter)

dbSNP: rs80358757

Total submissions: 8

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113422	SCV000282405	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-04-22	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	RCV000113422	SCV000327200	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV000496507	SCV001592419	pathogenic	Hereditary breast ovarian cancer syndrome	2023-03-17	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 51842). This variant is also known as 5572C>T. This premature translational stop signal has been observed in individual(s) with ovarian cancer and an increased risk of breast and/or ovarian cancer (PMID: 17148771, 29446198). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln1782*) 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).
National Health Laboratory Service, Universitas Academic Hospital and University of the Free State	RCV000496507	SCV002026116	pathogenic	Hereditary breast ovarian cancer syndrome	2021-11-16	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV003162380	SCV003877264	pathogenic	Hereditary cancer-predisposing syndrome	2022-11-22	criteria provided, single submitter	clinical testing	The p.Q1782* pathogenic mutation (also known as c.5344C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 5344. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This alteration has been identified in individuals diagnosed with breast, pancreatic and/or ovarian cancer (Zhang S et al. Gynecol Oncol, 2011 May;121:353-7; Xiong A et al. Am J Cancer Res, 2021 Sep;11:4551-4567; Van der Merwe NC et al. Front Genet, 2022 Apr;13:834265). 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). Of note, this alteration is also known as 5572C>T in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
Baylor Genetics	RCV003473360	SCV004210489	pathogenic	Familial cancer of breast	2022-09-24	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113422	SCV000146600	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2003-12-23	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496507	SCV000587762	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research