Submissions for variant NM_000059.4(BRCA2):c.9455_9456del (p.Glu3152fs)

dbSNP: rs80359764

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)	RCV000083160	SCV000301392	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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000083160	SCV000328137	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001682747	SCV001905626	pathogenic	not provided	2021-09-15	criteria provided, single submitter	clinical testing
Ambry Genetics	RCV002371881	SCV002687190	pathogenic	Hereditary cancer-predisposing syndrome	2021-03-27	criteria provided, single submitter	clinical testing	The c.9455_9456delAG pathogenic mutation, located in coding exon 24 of the BRCA2 gene, results from a deletion of two nucleotides at nucleotide positions 9455 to 9456, causing a translational frameshift with a predicted alternate stop codon (p.E3152Gfs*15). This mutation has been identified in several hereditary breast and ovarian cancer (HBOC) families (Pinto P et al. Breast Cancer Res Treat, 2016 Sep;159:245-56; Rebbeck TR et al. Hum Mutat, 2018 05;39:593-620; Capone GL et al. J Mol Diagn, 2018 01;20:87-94; Guindalini RSC et al. Clin Cancer Res, 2019 03;25:1786-1794; Laitman Y et al. Hum Mutat, 2019 11;40:e1-e23; Incorvaia L et al. Ther Adv Med Oncol, 2020 Dec;12:1758835920975326). 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	RCV002371881	SCV004362819	pathogenic	Hereditary cancer-predisposing syndrome	2021-10-19	criteria provided, single submitter	clinical testing	This variant deletes 2 nucleotides in exon 25 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 reported in two individuals affected with breast cancer (PMID: 10923033, 33403015) and has been identified in 2 families among the CIMBA participants (PMID: 29446198, 31209999). 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	RCV000496231	SCV005823499	pathogenic	Hereditary breast ovarian cancer syndrome	2025-01-29	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Glu3152Glyfs*15) 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 and/or ovarian cancer (PMID: 28888541, 30154229). For these reasons, this variant has been classified as Pathogenic.
Sharing Clinical Reports Project (SCRP)	RCV000083160	SCV000115234	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000083160	SCV000147640	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2002-05-29	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496231	SCV000588007	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research