Submissions for variant NM_000059.4(BRCA2):c.2287del (p.His763fs)

dbSNP: rs80359327

Total submissions: 11

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000077275	SCV000300505	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	RCV000575035	SCV000668609	pathogenic	Hereditary cancer-predisposing syndrome	2022-09-26	criteria provided, single submitter	clinical testing	The c.2287delC pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of one nucleotide at nucleotide position 2287, causing a translational frameshift with a predicted alternate stop codon (p.H763Mfs*9). This alteration has been reported in an individual diagnosed with ovarian cancer (Risch HA et al. J. Natl. Cancer Inst. 2006 Dec;98(23):1694-706; Zhang S et al. Gynecol. Oncol. 2011 May;121(2):353-7). Of note, this alteration is also known as 2515delC in published 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000496428	SCV000959884	pathogenic	Hereditary breast ovarian cancer syndrome	2024-09-15	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.His763Metfs*9) 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 ovarian cancer (PMID: 17148771, 21324516). This variant is also known as 2515delC. ClinVar contains an entry for this variant (Variation ID: 51266). For these reasons, this variant has been classified as Pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000575035	SCV001355368	pathogenic	Hereditary cancer-predisposing syndrome	2024-11-13	criteria provided, single submitter	clinical testing	This variant deletes 1 nucleotide in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. This variant has been observed in 2 individuals affected with ovarian cancer (PMID: 17148771, 21324516). This variant has not been identified in the general population by the Genome Aggregation Database (gnomAD). Loss of BRCA2 function is a known mechanism of disease (clinicalgenome.org). Based on the available evidence, this variant is classified as Pathogenic.
Mayo Clinic Laboratories, Mayo Clinic	RCV001509437	SCV001716146	pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing	PVS1, PM2, PP5
GeneDx	RCV001509437	SCV001824916	pathogenic	not provided	2023-09-18	criteria provided, single submitter	clinical testing	Frameshift variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss-of-function is a known mechanism of disease; Observed in individuals with BRCA2-related cancers (Risch et al., 2006; Zhang et al., 2011; Hu et al., 2018); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed at significant frequency in large population cohorts (gnomAD); Also known as 2515delC; This variant is associated with the following publications: (PMID: 21324516, 17148771, 29922827, 31948886, 31853058, 20104584)
Baylor Genetics	RCV003473312	SCV004211878	pathogenic	Familial cancer of breast	2023-12-04	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV001509437	SCV004219534	pathogenic	not provided	2021-09-09	criteria provided, single submitter	clinical testing	This frameshift variant causes the premature termination of BRCA2 protein synthesis. In addition, it has been reported in individuals with ovarian cancer and prostate cancer in the published literature (PMID: 17148771 (2006), 21324516 (2011), 31948886 (2020)). Based on the available information, this variant is classified as pathogenic.
Sharing Clinical Reports Project (SCRP)	RCV000077275	SCV000109072	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2012-01-09	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000077275	SCV000146025	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2002-06-20	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496428	SCV000587627	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research