Submissions for variant NM_000059.4(BRCA2):c.8323dup (p.Met2775fs)

dbSNP: rs276174904

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)	RCV000113901	SCV000301264	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	RCV000113901	SCV000327861	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Department of Medical Genetics, Oslo University Hospital	RCV000113901	SCV000605649	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-07-01	criteria provided, single submitter	clinical testing
GeneDx	RCV000520737	SCV000617960	pathogenic	not provided	2023-04-27	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; Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Not observed in large population cohorts (gnomAD); Observed in individuals with a personal and/or family history consistent with pathogenic variants in this gene (Heramb et al., 2018); Also known as 8551dupA; This variant is associated with the following publications: (PMID: 29339979, 27974384, 20104584, 31723001)
Ambry Genetics	RCV001017550	SCV001178643	pathogenic	Hereditary cancer-predisposing syndrome	2019-12-23	criteria provided, single submitter	clinical testing	The c.8323dupA pathogenic mutation, located in coding exon 17 of the BRCA2 gene, results from a duplication of A at nucleotide position 8323, causing a translational frameshift with a predicted alternate stop codon (p.M2775Nfs*7). In a large, clinic-based BRCA1/2 testing cohort in Norway, this variant was detected in 2 families (Heramb C et al. Hered Cancer Clin Pract, 2018 Jan;16:3). 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.
Clinical Genetics and Genomics, Karolinska University Hospital	RCV000520737	SCV001449706	pathogenic	not provided	2018-02-12	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV000113901	SCV001950099	likely pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2021-04-15	criteria provided, single submitter	clinical testing
Institute of Human Genetics, University of Leipzig Medical Center	RCV004804109	SCV005423801	pathogenic	Familial cancer of breast	2024-11-29	criteria provided, single submitter	clinical testing	Criteria applied: PVS1,PM5_STR,PM2_SUP
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113901	SCV000147318	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2009-09-24	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000496500	SCV000587945	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research
BRCAlab, Lund University	RCV000113901	SCV002588920	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2022-08-26	no assertion criteria provided	clinical testing