Submissions for variant NM_000059.4(BRCA2):c.6641dup (p.Tyr2215fs)

dbSNP: rs80359613

Total submissions: 14

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000031641	SCV000282433	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2016-04-22	reviewed by expert panel	curation	Variant allele predicted to encode a truncated non-functional protein.
Invitae	RCV000045004	SCV000073017	pathogenic	Hereditary breast ovarian cancer syndrome	2024-01-25	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Tyr2215Leufs*10) 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: 22366370, 22923021, 24156927). This variant is also known as c.6641insC (p.Thr2214Asnfs*10). ClinVar contains an entry for this variant (Variation ID: 38059). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000130476	SCV000185344	pathogenic	Hereditary cancer-predisposing syndrome	2022-09-20	criteria provided, single submitter	clinical testing	The c.6641dupC pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a duplication of C at position 6641, causing a translational frameshift with a predicted alternate stop codon within coding exon 10. This mutation has been reported in multiple families with hereditary breast and/or ovarian cancer (Levanat, S et al. Gene. 2012 May 1;498(2):169-76; Novakovic, S et al. Int J Oncol. 2012 Nov;41(5):1619-27; Rebbeck TR et al. Hum. Mutat. 2018 May;39(5):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.
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000031641	SCV000296601	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-10	criteria provided, single submitter	clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000031641	SCV000327481	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Color Diagnostics, LLC DBA Color Health	RCV000130476	SCV001342838	pathogenic	Hereditary cancer-predisposing syndrome	2023-09-06	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 11 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 multiple individuals with a personal or family history of prostate, breast, and/or ovarian cancer (PMID: 22366370, 24156927, 29446198, 33471991, doi.org/10.20471/LO.2023.51.01.02). 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.
Department of Molecular Diagnostics, Institute of Oncology Ljubljana	RCV001310133	SCV001499681	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 1	2020-04-02	criteria provided, single submitter	clinical testing
Sema4, Sema4	RCV000130476	SCV002536252	pathogenic	Hereditary cancer-predisposing syndrome	2021-12-09	criteria provided, single submitter	curation
Baylor Genetics	RCV003460524	SCV004213686	pathogenic	Familial cancer of breast	2023-08-09	criteria provided, single submitter	clinical testing
CeGaT Center for Human Genetics Tuebingen	RCV003992164	SCV004810672	pathogenic	not provided	2024-03-01	criteria provided, single submitter	clinical testing	BRCA2: PVS1, PM2, PS4:Moderate
All of Us Research Program, National Institutes of Health	RCV000031641	SCV004844287	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2023-10-23	criteria provided, single submitter	clinical testing	This variant inserts 1 nucleotide in exon 11 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 multiple individuals with a personal or family history of prostate, breast, and/or ovarian cancer (PMID: 22366370, 24156927, 29446198, 33471991, doi.org/10.20471/LO.2023.51.01.02). 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.
Sharing Clinical Reports Project (SCRP)	RCV000031641	SCV000054248	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2006-01-15	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000031641	SCV000146897	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2001-10-29	no assertion criteria provided	clinical testing
BRCAlab, Lund University	RCV000031641	SCV002588905	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2022-08-26	no assertion criteria provided	clinical testing