Submissions for variant NM_000059.4(BRCA2):c.8363G>A (p.Trp2788Ter)

dbSNP: rs80359080

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)	RCV000162060	SCV000301267	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000162060	SCV000296611	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-11-19	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000162060	SCV000327878	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV001017605	SCV001178708	pathogenic	Hereditary cancer-predisposing syndrome	2022-03-09	criteria provided, single submitter	clinical testing	The p.W2788* pathogenic mutation (also known as c.8363G>A), located in coding exon 18 of the BRCA2 gene, results from a G to A substitution at nucleotide position 8363. This changes the amino acid from a tryptophan to a stop codon within coding exon 18. This alteration has been reported in multiple high-risk breast and/or ovarian cancer families (Machackova E et al. BMC Cancer, 2008 May;8:140; Janaviius R et al. Cancer Genet, 2014 May;207:195-205; Polsler L et al. Eur. J. Hum. Genet. 2016 Feb;24(2):258-62) and has been reported to be a common BRCA2 mutation in Austria (Janaviius R. EPMA J, 2010 Sep;1:397-412). 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.
Color Diagnostics, LLC DBA Color Health	RCV001017605	SCV001345315	pathogenic	Hereditary cancer-predisposing syndrome	2020-01-15	criteria provided, single submitter	clinical testing	This variant changes 1 nucleotide in exon 19 of the BRCA2 gene, creating a premature translation stop signal. This variant is expected to result in an absent or non-functional protein product. 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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV001381657	SCV001580145	pathogenic	Hereditary breast ovarian cancer syndrome	2023-04-15	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: 52564). This premature translational stop signal has been observed in individual(s) with breast and/or ovarian cancer (PMID: 18489799, 25066507). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp2788*) 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).
Institute of Human Genetics, Medical University Innsbruck	RCV000162060	SCV000212030	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-02-11	no assertion criteria provided	clinical testing
CZECANCA consortium	RCV001271063	SCV001451885	pathogenic	Breast and/or ovarian cancer	2019-06-11	no assertion criteria provided	clinical testing
Laboratory of Urology, Hospital Clinic de Barcelona	RCV003332103	SCV004040505	pathogenic	Malignant tumor of urinary bladder		no assertion criteria provided	research