Submissions for variant NM_000059.4(BRCA2):c.9317G>A (p.Trp3106Ter)

dbSNP: rs80359205

Total submissions: 9

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000114090	SCV000301378	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	RCV000114090	SCV000328106	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
GeneKor MSA	RCV000585639	SCV000693593	pathogenic	Familial cancer of breast	2020-01-01	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal at codon 3106 of the BRCA2 protein. It is expected to result in an absent or disrupted protein product. Truncating mutations in BRCA2 are known to be pathogenic. This variant is listed in the mutation database ClinVar (Variation ID: 52814/).
Ambry Genetics	RCV001019163	SCV001180486	pathogenic	Hereditary cancer-predisposing syndrome	2019-04-25	criteria provided, single submitter	clinical testing	The p.W3106* pathogenic mutation (also known as c.9317G>A), located in coding exon 24 of the BRCA2 gene, results from a G to A substitution at nucleotide position 9317. This changes the amino acid from a tryptophan to a stop codon within coding exon 24. This alteration was reported in an Iranian male diagnosed with breast cancer (Zorrieh Zahra A et al. Int J Mol Cell Med. 2016 May;5:114-22), a male diagnosed with Gleason 7 prostate cancer (Ibrahim M et al. BMC Cancer 2018 02;18:179), and in multiple cohorts of Chinese breast cancer patients (Zhang J et al. Breast Cancer Res. Treat. 2016 08;158:455-62; Sun J et al. Clin. Cancer Res. 2017 Oct;23:6113-6119; Liang Y et al. Med. Sci. Monit. 2018 Apr;24:2465-2475; Bhaskaran SP et al. Int. J. Cancer 2019 Jan). 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.
Invitae	RCV000496936	SCV002243795	pathogenic	Hereditary breast ovarian cancer syndrome	2022-03-12	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: 52814). This premature translational stop signal has been observed in individual(s) with with clinical features of hereditary breast and ovarian cancer syndrome (PMID: 27257965, 27478808, 28724667, 30702160). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp3106*) 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).
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV000585639	SCV004697502	pathogenic	Familial cancer of breast	2024-02-27	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000114090	SCV000147610	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	RCV000496936	SCV000587998	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
Medical Genetics Laboratory, Umraniye Training and Research Hospital, University of Health Sciences	RCV001646927	SCV001860289	pathogenic	Breast carcinoma	2021-09-11	no assertion criteria provided	clinical testing