Submissions for variant NM_000059.4(BRCA2):c.5799_5802del (p.Asn1933fs)

dbSNP: rs80359538

Total submissions: 19

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA)	RCV000113485	SCV000300935	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.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000044761	SCV000072774	pathogenic	Hereditary breast ovarian cancer syndrome	2025-01-11	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Asn1933Lysfs*29) 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 a personal and/or family history of breast and/or ovarian cancer (PMID: 15131399, 22682623, 26681312, 28008555). This variant is also known as 6027del4. ClinVar contains an entry for this variant (Variation ID: 37998). For these reasons, this variant has been classified as Pathogenic.
Ambry Genetics	RCV000131107	SCV000186037	pathogenic	Hereditary cancer-predisposing syndrome	2025-01-15	criteria provided, single submitter	clinical testing	The c.5799_5802delCCAA pathogenic mutation, located in coding exon 10 of the BRCA2 gene, results from a deletion of 4 nucleotides at nucleotide positions 5799 to 5802, causing a translational frameshift with a predicted alternate stop codon (p.N1933Kfs*29). This variant has been reported in multiple breast and/or ovarian cancer families (Lubinski J et al. Fam. Cancer. 2004;3:1-10; Dutil J et al. Cancer Genet. 2012 May;205:242-8; Wong E et al. Genomic Medicine. 2016 Jan;1:15003; Pritzlaff M et al. Breast Cancer Res. Treat. 2017 Feb;161:575-586). Of note, this alteration is also designated as 6027del4 in published literature. This variant is considered to be rare based on population cohorts in the Genome Aggregation Database (gnomAD). 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.
GeneDx	RCV000160298	SCV000210770	pathogenic	not provided	2023-12-07	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; Observed in individuals with a personal or family history consistent with pathogenic variants in this gene (PMID: 22682623, 28495237, 28008555); Not observed at significant frequency in large population cohorts (gnomAD); Truncating variants in this gene are considered pathogenic by a well-established clinical consortium and/or database; Also known as 6027_6030delCCAA or 6027del4; This variant is associated with the following publications: (PMID: 22109874, 31794323, 34413315, 28888541, 15131399, 22682623, 26681312, 28008555, 28127413, 28495237, 26556299, 30787465, 31892343, 30322717, 26221963, 30068706, 29263802, 29308099)
Eurofins Ntd Llc (ga)	RCV000160298	SCV000225164	pathogenic	not provided	2015-04-20	criteria provided, single submitter	clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano	RCV000160298	SCV000296582	pathogenic	not provided	2024-06-21	criteria provided, single submitter	clinical testing	The BRCA2 c.5799_5802del (p.Asn1933Lysfs*29) variant alters the translational reading frame of the BRCA2 mRNA and causes the premature termination of BRCA2 protein synthesis. This variant has been reported in the published literature in individuals and families with breast and/or ovarian cancer (PMID: 34413315 (2021), 30322717 (2018), 29446198 (2018), 28888541 (2017), 28008555 (2017), 29263802 (2016), 22682623 (2012), 15131399 (2004)). Additionally, this variant has been reported in individuals with endometrial and colon cancer (PMID: 28495237 (2017)), uterine cancer (PMID: 26556299 (2016)), bladder cancer (PMID: 31794323 (2020)), and anal cancer (PMID: 26681312 (2015)). This variant has not been reported in large, multi-ethnic general populations (Genome Aggregation Database, http://gnomad.broadinstitute.org). Based on the available information, this variant is classified as pathogenic.
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge	RCV000113485	SCV000327285	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-10-02	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV000472040	SCV000541013	pathogenic	Familial cancer of breast	2023-11-28	criteria provided, single submitter	clinical testing
Counsyl	RCV000113485	SCV000677690	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2015-11-03	criteria provided, single submitter	clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp	RCV000044761	SCV000694904	pathogenic	Hereditary breast ovarian cancer syndrome	2019-03-04	criteria provided, single submitter	clinical testing	Variant summary: BRCA2 c.5799_5802delCCAA (p.Asn1933LysfsX29) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Other truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 245780 control chromosomes. c.5799_5802delCCAA has been reported in the literature in multiple individuals affected with Hereditary Breast and Ovarian Cancer. These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Nine clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was classified as pathogenic.
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	RCV000160298	SCV001472633	pathogenic	not provided	2019-10-24	criteria provided, single submitter	clinical testing	The BRCA2 c.5799_5802delCCAA; p.Asn1933fs variant (rs80359538), also known as 6027del4 in alternative nomenclature, is reported in the literature in several individuals with a personal and/or family history of breast cancer (Dutil 2012, Pritzlaff 2017). This variant is absent from general population databases (Exome Variant Server, Genome Aggregation Database), indicating it is not a common polymorphism, and it is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 37998). This variant causes a frameshift by deleting four nucleotides, so it is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on available information, this variant is considered to be pathogenic. References: Dutil J et al. Identification of the prevalent BRCA1 and BRCA2 mutations in the female population of Puerto Rico. Cancer Genet. 2012 May;205(5):242-8. Pritzlaff M et al. Male breast cancer in a multi-gene panel testing cohort: insights and unexpected results. Breast Cancer Res Treat. 2017 Feb;161(3):575-586.
Sema4, Sema4	RCV000131107	SCV002536176	pathogenic	Hereditary cancer-predisposing syndrome	2022-01-20	criteria provided, single submitter	curation
New York Genome Center	RCV000113485	SCV002548613	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2021-08-06	criteria provided, single submitter	clinical testing	The BRCA2 c.5799_5802del, p.Asn1933LysfsTer29 variant, also known as 6027del4 in alternative nomenclature, is reported in the literature in several individuals with a personal and/or family history of breast cancer (PMID: 22682623, 28008555). This variant is absent from the gnomAD v3.1.1 database, suggesting it is not a common benign variant in the populations represented in this database. This variant causes a frameshift by deleting four nucleotides, which is predicted to result in atruncated protein or mRNA subject to nonsense-mediated decay. Based on the available evidence, c.5799_5802del, p.Asn1933LysfsTer29 variant in the BRCA2 gene is classified as pathogenic.
Color Diagnostics, LLC DBA Color Health	RCV000131107	SCV004362127	pathogenic	Hereditary cancer-predisposing syndrome	2024-12-11	criteria provided, single submitter	clinical testing	This variant deletes 4 nucleotides in exon 11 of the BRCA2 gene, creating a frameshift and premature translation stop signal. This variant is also known as 6072del4 in the literature. This variant is expected to result in an absent or non-functional protein product. This variant has been reported in several individuals affected with breast or ovarian cancer (PMID: 22682623, 26221963, 28008555, 29263802, 29308099, 30322717). This variant has also been reported in six suspected hereditary breast and ovarian cancer families (PMID: 15131399, 29446198). A multifactorial analysis has reported a likelihood ratio for pathogenicity based on personal and family history of 323.27 from log(LR)=2.509565353 for 7 carriers (PMID: 31853058). 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.
All of Us Research Program, National Institutes of Health	RCV004803051	SCV005424502	pathogenic	BRCA2-related cancer predisposition	2024-09-28	criteria provided, single submitter	clinical testing	The c.5799_5802del (p.Asn1933Lysfs*29) variant in the BRCA2 gene is located on the exon 11 and is predicted to cause shift of reading frame that introduces a premature translation termination codon (p.Asn1933Lysfs*29), resulting in an absent or disrupted protein product. The variant has been reported in individuals with breast/ovarian/urothelial/endometrial cancer (PMID: 29263802, 32064343, 28008555, 31794323, 30068706). Loss-of-function variants of BRCA2 are known to be pathogenic (PMID: 8988179, 11897832, 29446198). Other frameshift/truncating variants in the same exon have been reviewed as pathogenic (p.Tyr1894*, p.Ser1951fs, ClinVar ID: 37989, 38001). The variant is reported in ClinVar as pathogenic (ID: 37998) and reviewed by the expert panel. The variant is absent in the general population database (gnomAD). Therefore, the c.5799_5802del (p.Asn1933Lysfs*29) variant of BRCA2 has been classified as pathogenic.
Fulgent Genetics, Fulgent Genetics	RCV005007910	SCV005633940	pathogenic	Familial cancer of breast; Breast-ovarian cancer, familial, susceptibility to, 2; Fanconi anemia complementation group D1; Medulloblastoma; Wilms tumor 1; Pancreatic cancer, susceptibility to, 2; Glioma susceptibility 3; Familial prostate cancer	2024-05-14	criteria provided, single submitter	clinical testing
Sharing Clinical Reports Project (SCRP)	RCV000113485	SCV000054185	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2012-05-01	no assertion criteria provided	clinical testing
Breast Cancer Information Core (BIC) (BRCA2)	RCV000113485	SCV000146702	pathogenic	Breast-ovarian cancer, familial, susceptibility to, 2	2004-02-20	no assertion criteria provided	clinical testing
Research Molecular Genetics Laboratory, Women's College Hospital, University of Toronto	RCV000044761	SCV000587801	pathogenic	Hereditary breast ovarian cancer syndrome	2014-01-31	no assertion criteria provided	research