Submissions for variant NM_000059.4(BRCA2):c.9100C>T (p.Gln3034Ter)

dbSNP: rs80359163

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)	RCV000114047	SCV000301353	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.
GeneDx	RCV000220911	SCV000278885	pathogenic	not provided	2022-09-30	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (Jian 2017, Sun 2017, Rebbeck 2018, Li 2019); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed in large population cohorts (gnomAD); Also known as 9328C>T; This variant is associated with the following publications: (PMID: 29446198, 22632462, 28724667, 29093764, 29752822, 31825140, 30702160, 29922827)
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000114047	SCV000328049	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Invitae	RCV000496303	SCV001579242	pathogenic	Hereditary breast ovarian cancer syndrome	2023-08-10	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 52749). This premature translational stop signal has been observed in individual(s) with a personal and/or family history of breast cancer (PMID: 28724667, 29446198, 29752822). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Gln3034*) 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).
Molecular Endocrinology Laboratory, Christian Medical College	RCV000114047	SCV002003993	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2		criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002371870	SCV002684187	pathogenic	Hereditary cancer-predisposing syndrome	2022-01-27	criteria provided, single submitter	clinical testing	The p.Q3034* pathogenic mutation (also known as c.9100C>T), located in coding exon 22 of the BRCA2 gene, results from a C to T substitution at nucleotide position 9100. This changes the amino acid from a glutamine to a stop codon within coding exon 22. This alteration has been identified in individuals diagnosed with breast and pancreatic cancer (Jian W et al. Hered Cancer Clin Pract, 2017 Oct;15:19; Sun J et al. Clin Cancer Res, 2017 Oct;23:6113-6119; Hu C et al. JAMA, 2018 06;319:2401-2409; Wei H et al. Oncol Lett, 2018 Jun;15:9420-9428; Li JY et al. Int J Cancer, 2019 01;144:281-289). 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). 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	RCV003473428	SCV004210517	pathogenic	Familial cancer of breast	2022-08-11	criteria provided, single submitter	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000114047	SCV000147536	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	RCV000496303	SCV000587987	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research