ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5350_5351del (p.Asn1784fs) (rs80359507)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 21
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000074537 SCV000883477 pathogenic not provided 2018-03-13 criteria provided, single submitter clinical testing The c.5350_5351delAA; p.Asn1784fs variant (rs80359507) has been identified in multiple patients diagnosed with ovarian, fallopian tube or peritoneal cancer (Gayther 1997, Walsh 2011, Zhang 2011, Cunningham 2014). It is reported as pathogenic by multiple laboratories in ClinVar (Variation ID: 37959) and observed in only 1/30754 alleles in the Genome Aggregation Database. This variant causes a frameshift by deleting 2 nucleotides, so is predicted to result in a truncated protein or mRNA subject to nonsense-mediated decay. Based on the above information, this variant is considered pathogenic. References: Cunningham J et al. Clinical characteristics of ovarian cancer classified by BRCA1, BRCA2, and RAD51C status. Sci Rep. 2014. 4:4026. Gayther S et al. Variation of risks of breast and ovarian cancer associated with different germline mutations of the BRCA2 gene. Nat Genet. 1997. 15(1):103-5. Walsh T et al. Mutations in 12 genes for inherited ovarian, fallopian tube, and peritoneal carcinoma identified by massively parallel sequencing.Proc Natl Acad Sci U S A. 2011. 108(44):18032-7. Zhang S et al. Frequencies of BRCA1 and BRCA2 mutations among 1,342 unselected patients with invasive ovarian cancer.Gynecol Oncol. 2011. 121(2):353-7.
Ambry Genetics RCV000131110 SCV000186040 pathogenic Hereditary cancer-predisposing syndrome 2018-02-26 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Alterations resulting in premature truncation (e.g.reading frame shift, nonsense)
Breast Cancer Information Core (BIC) (BRCA2) RCV000031540 SCV000146602 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131110 SCV000683699 pathogenic Hereditary cancer-predisposing syndrome 2015-03-10 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031540 SCV000327201 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Counsyl RCV000031540 SCV000677682 pathogenic Breast-ovarian cancer, familial 2 2015-07-08 criteria provided, single submitter clinical testing
DNA and Cytogenetics Diagnostics Unit,Erasmus Medical Center RCV000031540 SCV000744468 pathogenic Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000044639 SCV000591962 pathogenic Hereditary breast and ovarian cancer syndrome 2014-07-16 criteria provided, single submitter clinical testing
Diagnostic Laboratory, Department of Genetics,University Medical Center Groningen RCV000031540 SCV000733267 pathogenic Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031540 SCV000282406 pathogenic Breast-ovarian cancer, familial 2 2016-04-22 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
GeneDx RCV000074537 SCV000108622 pathogenic not provided 2018-09-11 criteria provided, single submitter clinical testing This deletion of two nucleotides is denoted BRCA2 c.5350_5351delAA at the cDNA level and p.Asn1784HisfsX2 (N1784HfsX2) at the protein level. The normal sequence, with the bases that are deleted in brackets, is CAAAAA[delAA]CACT. The deletion causes a frameshift, changing an Asparagine to a Histidine at codon 1784, and creates a premature stop codon at position 2 of the new reading frame. BRCA2 c.5350_5351delAA is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. This variant, previously denoted as BRCA2 5573delAA or 5578delAA using alternate nomenclature, has been reported in association with breast, ovarian, and prostate cancer (Gayther 1997, Walsh 2011, Zhang 2011, Castro 2013, Cunningham 2014). We consider this variant to be pathogenic.
HudsonAlpha Institute for Biotechnology, HudsonAlpha Institute for Biotechnology RCV000031540 SCV000993555 pathogenic Breast-ovarian cancer, familial 2 2018-09-07 criteria provided, single submitter research
Human Genome Sequencing Center Clinical Lab,Baylor College of Medicine RCV000031540 SCV000839933 pathogenic Breast-ovarian cancer, familial 2 2018-02-25 criteria provided, single submitter clinical testing This c.5350_5351delAA (p.Asn1784Hisfs*2) frameshift variant in the BRCA2 gene is predicted to introduce a premature translation termination codon and has been reported in multiple unrelated individuals with breast, ovarian, prostate, fallopian, and/or peritoneal cancer (PMID: 8988179, 21324516, 22006311, 23569316, 23633455, 24504028). The c.5350_5351delAA (p.Asn1784Hisfs*2) variant in the BRCA2 gene is classified as pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044639 SCV000694862 pathogenic Hereditary breast and ovarian cancer syndrome 2016-05-02 criteria provided, single submitter clinical testing Variant summary: The c.5350_5351delAA variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein, which is a commonly known mechanism for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g.c.5386_5387delGA/p.Asp1796fs). One in-silico tool predicts damaging outcome for this variant. This variant is absent in 122212 control chromosomes. In addition, multiple clinical laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant was classified as pathogenic.
Invitae RCV000044639 SCV000072652 pathogenic Hereditary breast and ovarian cancer syndrome 2019-01-08 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Asn1784Hisfs*2) in the BRCA2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been reported in individuals affected with breast and/or ovarian cancer (PMID: 10923033, 22144684, 21324516, 22006311, 23633455). This variant is also known as 5573delAA and 5578delAA in the literature. ClinVar contains an entry for this variant (Variation ID: 37959). Loss-of-function variants in BRCA2 are known to be pathogenic (PMID: 20104584). For these reasons, this variant has been classified as Pathogenic.
Laboratory for Molecular Medicine,Partners HealthCare Personalized Medicine RCV000044639 SCV000605783 pathogenic Hereditary breast and ovarian cancer syndrome 2015-12-15 criteria provided, single submitter clinical testing The p.Asn1784fs variant in BRCA2 has been identified in greater than 30 individu als with BRCA2 associated cancers (Gayther 1997, Walsh 2011, Zhang 2011, George 2013, Cunningham 2014, Breast Cancer Information Core (BIC) database, Sharing Cl inical Reports Project). This variant has been identified in 1/66234 of European chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinstitu te.org; dbSNP rs80359507). This variant is predicted to cause a frameshift, whic h alters the protein?s amino acid sequence beginning at position 1784 and leads to a premature termination codon 2 amino acids downstream. This alteration is th en predicted to lead to a truncated or absent protein. Heterozygous loss of func tion of the BRCA2 gene is an established disease mechanism in individuals with h ereditary breast and ovarian cancer (HBOC). In summary, this variant meets our c riteria to be classified as pathogenic for HBOC in an autosomal dominant manner based upon the predicted impact to the protein.
Mayo Clinic Genetic Testing Laboratories,Mayo Clinic RCV000074537 SCV000778684 pathogenic not provided 2017-12-12 no assertion criteria provided clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000031540 SCV000195990 pathogenic Breast-ovarian cancer, familial 2 2014-11-03 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000074537 SCV000296699 pathogenic not provided 2015-03-28 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044639 SCV000587763 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031540 SCV000054145 pathogenic Breast-ovarian cancer, familial 2 2012-07-17 no assertion criteria provided clinical testing

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.