Submissions for variant NM_000059.4(BRCA2):c.6202dup (p.Ile2068fs)

dbSNP: rs397507833

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000162057	SCV000300997	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	RCV000129495	SCV000184267	pathogenic	Hereditary cancer-predisposing syndrome	2016-12-21	criteria provided, single submitter	clinical testing	The c.6202dupA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a duplication of A at nucleotide position 6202, causing a translational frameshift with a predicted alternate stop codon (p.I2068Nfs*10). This mutation was described in an Italian family with three females diagnosed with breast cancer prior to age 50 and one female diagnosed at age 57 (Santarosa M et al. Int. J. Cancer 1999; 83:5-9). This mutation was also identified in the germline of 1/47 high-grade serous ovarian carcinoma samples in a study of next-generation tumor sequencing (Mafficini A et al. Oncotarget, 2016 Jan;7:1076-83). 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.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000162057	SCV000327365	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Labcorp Genetics (formerly Invitae), Labcorp	RCV001388245	SCV001589157	pathogenic	Hereditary breast ovarian cancer syndrome	2019-06-04	criteria provided, single submitter	clinical testing	For these reasons, this variant has been classified as Pathogenic. Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). This variant has been observed in individuals affected with or undergoing testing for hereditary breast and/or ovarian cnacer (PMID: 10449599, 26745875, 26014432, 29446198). This variant is also known as c.6431insA in the literature. ClinVar contains an entry for this variant (Variation ID: 52030). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Ile2068Asnfs*10) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product.
Institute of Human Genetics, Medical University Innsbruck	RCV000162057	SCV000212025	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-02-11	no assertion criteria provided	clinical testing
Department of Pathology and Laboratory Medicine, Sinai Health System	RCV001354867	SCV001549582	uncertain significance	not provided		no assertion criteria provided	clinical testing