Submissions for variant NM_000059.4(BRCA2):c.3778_3779del (p.Leu1260fs)

dbSNP: rs397507686

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000256856	SCV000324185	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-10-18	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	RCV000256856	SCV000326912	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496308	SCV001581571	pathogenic	Hereditary breast ovarian cancer syndrome	2022-09-20	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: 51523). This variant is also known as 4005delTT. This premature translational stop signal has been observed in individual(s) with ovarian cancer (PMID: 17148771, 21324516). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Leu1260Ilefs*4) 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).
Sema4, Sema4	RCV002257386	SCV002533821	pathogenic	Hereditary cancer-predisposing syndrome	2021-09-09	criteria provided, single submitter	curation
Ambry Genetics	RCV002257386	SCV005026561	pathogenic	Hereditary cancer-predisposing syndrome	2023-10-06	criteria provided, single submitter	clinical testing	The c.3778_3779delTT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 3778 to 3779, causing a translational frameshift with a predicted alternate stop codon (p.L1260Ifs*4). This variant has been identified in individuals with a personal history of ovarian or prostate cancer (Risch HA et al. J Natl Cancer Inst, 2006 Dec;98:1694-706; Zhang S et al. Gynecol Oncol, 2011 May;121:353-7; Nguyen-Dumont T et al. Int J Cancer, 2020 Oct;147:2142-2149). This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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	RCV000496308	SCV000587681	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research