Submissions for variant NM_000059.4(BRCA2):c.9294C>A (p.Tyr3098Ter)

dbSNP: rs80359200

Total submissions: 10

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031811	SCV000301375	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	RCV000031811	SCV000328101	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Counsyl	RCV000031811	SCV000786350	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2018-04-16	criteria provided, single submitter	clinical testing
Equipe Genetique des Anomalies du Developpement, Université de Bourgogne	RCV000031811	SCV000965835	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-01-01	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496360	SCV001578430	pathogenic	Hereditary breast ovarian cancer syndrome	2023-02-16	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr3098*) 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 a personal or family history of BRCA2-related cancer (PMID: 15131399, 29446198). This variant is also known as 9522C>A. ClinVar contains an entry for this variant (Variation ID: 38228). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV002371799	SCV002686675	pathogenic	Hereditary cancer-predisposing syndrome	2023-03-30	criteria provided, single submitter	clinical testing	The p.Y3098* pathogenic mutation (also known as c.9294C>A), located in coding exon 24 of the BRCA2 gene, results from a C to A substitution at nucleotide position 9294. This changes the amino acid from a tyrosine to a stop codon within coding exon 24. This mutation has been reported in serous ovarian cancer patients (Labidi-Galy SI et al. Clin. Cancer Res. 2018 Jan;24:326-333), and in several Chinese breast cancer patients (Sun J et al. Clin. Cancer Res. 2017 Oct;23:6113-6119; Wen WX et al. J. Med. Genet. 2018 Feb;55:97-103). 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.
Neuberg Centre For Genomic Medicine, NCGM	RCV000031811	SCV004047722	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2		criteria provided, single submitter	clinical testing	The stop gained (c.9294C>A) variant has been reported previously in patients affected with Breast-ovarian cancer, familial, 2 (Lubinski et. al., 2004; Rebbeck et. al., 2018). The c.9294C>A variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. This variant has been reported to the ClinVar database as Pathogenic. The nucleotide change c.9294C>A in BRCA2 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. This variant is predicted to cause loss of normal protein function through protein truncation. Loss-of-function variants in BRCA2 are known to be pathogenic (Borg et. al., 2010). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP)	RCV000031811	SCV000054419	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2011-10-25	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031811	SCV000147603	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496360	SCV000587996	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research