Submissions for variant NM_000059.4(BRCA2):c.2743_2747del (p.Thr915fs)

dbSNP: rs786204752

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)	RCV000169607	SCV000300554	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.
Counsyl	RCV000169607	SCV000221129	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-02-11	criteria provided, single submitter	literature only
GeneKor MSA	RCV000239268	SCV000296817	pathogenic	Familial cancer of breast	2020-01-01	criteria provided, single submitter	clinical testing	This variant is a 5 bp deletion at amino acid residue 915 of the BRCA2 gene. It results in a frame-shift creating an unrecognizable protein after amino acid 915 and a new stop codon 19 amino acid residues later, thus resulting in a truncated protein product.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000169607	SCV000326751	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000239268	SCV000541007	pathogenic	Familial cancer of breast	2017-02-23	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000759592	SCV000889009	pathogenic	not provided	2018-02-13	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496389	SCV001585162	pathogenic	Hereditary breast ovarian cancer syndrome	2023-07-07	criteria provided, single submitter	clinical testing	This premature translational stop signal has been observed in individual(s) with personal or family history of breast and/or ovarian cancer (PMID: 24156927, 29446198). For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 189178). This variant is present in population databases (rs757377991, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Thr915Cysfs*19) 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).
Ambry Genetics	RCV002433727	SCV002749418	pathogenic	Hereditary cancer-predisposing syndrome	2022-07-15	criteria provided, single submitter	clinical testing	The c.2743_2747delACTTG pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of 5 nucleotides at nucleotide positions 2743 to 2747, causing a translational frameshift with a predicted alternate stop codon (p.T915Cfs*19). This alteration has been identified amongst multiple patients with a personal history of pancreatic adenocarcinoma and/or breast cancer (Yin L et al. JAMA Netw Open, 2022 02;5:e2148721; Torres-Mejía G et al. Cancer Epidemiol Biomarkers Prev, 2015 Mar;24:498-505; Muendlein A et al. J Cancer Res Clin Oncol, 2015 Nov;141:2005-12Bang YJ et al. Cancer Res Treat, 2021 Oct; Golan T et al. J Clin Oncol, 2020 05;38:1442-1454). This alteration has been referred to as BRCA2 2971del5 within the literature. 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	RCV000496389	SCV000587641	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research