Submissions for variant NM_000059.4(BRCA2):c.8145del (p.Val2716fs)

dbSNP: rs1135401923

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)	RCV000576569	SCV000784061	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.
Counsyl	RCV000576569	SCV000677857	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-12-12	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002420265	SCV002680296	pathogenic	Hereditary cancer-predisposing syndrome	2021-11-18	criteria provided, single submitter	clinical testing	The c.8145delA pathogenic mutation, located in coding exon 17 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 8145, causing a translational frameshift with a predicted alternate stop codon (p.V2716Wfs*17). 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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV002475981	SCV002774270	likely pathogenic	not provided	2021-07-14	criteria provided, single submitter	clinical testing	This frameshift variant is predicted to cause the premature termination of BRCA2 protein synthesis. To the best of our knowledge, the variant has not been reported in the published literature. Based on the available information, this variant is classified as likely pathogenic.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496937	SCV004678572	pathogenic	Hereditary breast ovarian cancer syndrome	2022-12-05	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Val2716Trpfs*17) 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: 431341). For these reasons, this variant has been classified as Pathogenic.
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496937	SCV000587935	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research