Submissions for variant NM_000059.4(BRCA2):c.8009C>A (p.Ser2670Ter)

dbSNP: rs80359035

Total submissions: 7

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000239017	SCV000324610	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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000239017	SCV000296564	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-02-27	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000239017	SCV000327795	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV000569299	SCV000661413	pathogenic	Hereditary cancer-predisposing syndrome	2019-04-16	criteria provided, single submitter	clinical testing	The p.S2670* pathogenic mutation (also known as c.8009C>A), located in coding exon 17 of the BRCA2 gene, results from a C to A substitution at nucleotide position 8009. This changes the amino acid from a serine to a stop codon within coding exon 17. This mutation was identified in a hereditary breast cancer family (Sinilnikova OM et al. Fam. Cancer, 2006;5:15-20) and one study demonstrated that this mutation triggered nonsense-mediated mRNA decay (Ware MD et al. Oncogene, 2006 Jan;25:323-8). This alteration was identified in a large, worldwide study of BRCA1/2 mutation positive families (Rebbeck TR et al. Hum. Mutat. 2018 05;39:593-620). 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	RCV000496340	SCV001587431	pathogenic	Hereditary breast ovarian cancer syndrome	2024-04-17	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Ser2670*) 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 breast cancer (PMID: 16528604). ClinVar contains an entry for this variant (Variation ID: 52470). Studies have shown that this premature translational stop signal alters mRNA splicing and is expected to lead to the loss of protein expression (PMID: 28339459). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP)	RCV000239017	SCV000297560	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2006-10-30	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496340	SCV000587930	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research