Submissions for variant NM_000059.4(BRCA2):c.5266_5269del (p.Val1756fs)

dbSNP: rs80359501

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)	RCV000031536	SCV000300854	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.
Ambry Genetics	RCV004948139	SCV005547561	pathogenic	Hereditary cancer-predisposing syndrome	2024-11-14	criteria provided, single submitter	clinical testing	The c.5266_5269delGTAT pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of 4 nucleotides at nucleotide positions 5266 to 5269, causing a translational frameshift with a predicted alternate stop codon (p.V1756Ifs*20). 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496495	SCV005823532	pathogenic	Hereditary breast ovarian cancer syndrome	2024-10-09	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val1756Ilefs*20) 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 variant has not been reported in the literature in individuals affected with BRCA2-related conditions. ClinVar contains an entry for this variant (Variation ID: 37955). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP)	RCV000031536	SCV000054141	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2008-03-24	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031536	SCV000146584	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2001-10-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496495	SCV000587756	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research