Submissions for variant NM_000059.4(BRCA2):c.3883C>T (p.Gln1295Ter)

dbSNP: rs879255309

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000661418	SCV000783694	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2017-12-15	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000239260	SCV000296579	pathogenic	not provided	2018-12-12	criteria provided, single submitter	clinical testing	The variant creates a premature nonsense codon, and is therefore predicted to result in the loss of a functional protein. Found in at least one symptomatic patient, and not found in general population data.
Yang An-Suei Laboratory, Academia Sinica	RCV000504604	SCV000583415	pathogenic	Breast neoplasm		criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496728	SCV000759181	pathogenic	Hereditary breast ovarian cancer syndrome	2022-01-27	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Gln1295*) 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 family or personal history of breast and/or ovarian cancer (PMID: 28724667, 29435039, 29566657, 29752822). ClinVar contains an entry for this variant (Variation ID: 252424). For these reasons, this variant has been classified as Pathogenic.
Cancer Molecular Diagnostics Core, Tianjin Medical University Cancer Institute and Hospital	RCV000656471	SCV000778341	likely pathogenic	Breast cancer, susceptibility to	2018-03-25	criteria provided, single submitter	research
Ambry Genetics	RCV001021351	SCV001182958	pathogenic	Hereditary cancer-predisposing syndrome	2024-05-14	criteria provided, single submitter	clinical testing	The p.Q1295* pathogenic mutation (also known as c.3883C>T), located in coding exon 10 of the BRCA2 gene, results from a C to T substitution at nucleotide position 3883. This changes the amino acid from a glutamine to a stop codon within coding exon 10. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). This mutation has been reported in Chinese hereditary breast/ovarian cancer cohorts (Sun J et al. Clin. Cancer Res. 2017 Oct;23:6113-6119; Fang M et al. Oncol. Lett. 2018 Mar;15:3068-3074; Wang YA et al. BMC Cancer 2018 03;18:315; Li JY et al. Int. J. Cancer 2019 Jan;144:281-289). 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.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496728	SCV000587688	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research