ClinVar Miner

Submissions for variant NM_000059.3(BRCA2):c.5410_5411del (p.Val1804fs) (rs80359512)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 14
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000131109 SCV000186039 pathogenic Hereditary cancer-predisposing syndrome 2017-10-24 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) RCV000031544 SCV000146609 pathogenic Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
Color RCV000131109 SCV000911345 pathogenic Hereditary cancer-predisposing syndrome 2018-06-18 criteria provided, single submitter clinical testing
Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA), c/o University of Cambridge RCV000031544 SCV000327215 pathogenic Breast-ovarian cancer, familial 2 2015-10-02 criteria provided, single submitter clinical testing
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031544 SCV000300872 pathogenic Breast-ovarian cancer, familial 2 2016-09-08 reviewed by expert panel curation Variant allele predicted to encode a truncated non-functional protein.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735564 SCV000863702 pathogenic Breast and/or ovarian cancer 2010-06-28 no assertion criteria provided clinical testing
GeneDx RCV000219181 SCV000278860 pathogenic not provided 2018-02-16 criteria provided, single submitter clinical testing This deletion of 2 nucleotides in BRCA2 is denoted c.5410_5411delGT at the cDNA level and p.Val1804LysfsX2 (V1804KfsX2) at the protein level. The normal sequence, with the bases that are deleted in brackets, is AACT[delGT]AAAT. The deletion causes a frameshift, which changes a Valine to a Lysine at codon 1804, and creates a premature stop codon at position 2 of the new reading frame. This variant is predicted to cause loss of normal protein function through either protein truncation or nonsense-mediated mRNA decay. BRCA2 c.5410_5411delGT, previously reported as BRCA2 5638delGT using alternate nomenclature, has been observed in individuals and families with breast and/or ovarian cancer as well as in a woman with pancreatic cancer (Euhus 2002, Marroni 2004, Johns 2014, Meeks 2016). We consider this variant to be pathogenic.
Integrated Genetics/Laboratory Corporation of America RCV000044655 SCV000694866 pathogenic Hereditary breast and ovarian cancer syndrome 2016-08-24 criteria provided, single submitter clinical testing Variant summary: The BRCA2 c.5410_5411delGT (p.Val1804Lysfs) variant results in a premature termination codon, predicted to cause a truncated or absent BRCA2 protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory (e.g. c.5542delA/p.Ser1848fs). One in silico tool predicts a damaging outcome for this variant. This variant was absent in 121092 control chromosomes. This variant has been reported in multiple HBOC patients and multiple clinical diagnostic laboratories/reputable databases classified this variant as pathogenic. Taken together, this variant is classified as pathogenic.
Invitae RCV000044655 SCV000072668 pathogenic Hereditary breast and ovarian cancer syndrome 2018-12-04 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Val1804Lysfs*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 the literature in individuals with breast and/or ovarian cancer (PMID: 15340362) and pancreatic cancer (PMID: 24963353). This variant is also known as 5638delGT in the literature. ClinVar contains an entry for this variant (Variation ID: 37963). 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 RCV000044655 SCV000605822 pathogenic Hereditary breast and ovarian cancer syndrome 2017-07-20 criteria provided, single submitter clinical testing The p.Val1804fs variant in BRCA2 has been reported in 6 individuals with heredit ary breast and/or ovarian cancer (HBOC; Marroni 2004, Breast Cancer Information Core (BIC) database; https://research.nhgri.nih.gov/projects/bic/) and was absen t from large population studies, though the ability of these studies to accurate ly detect indels may be limited. This variant is predicted to cause a frameshift , which alters the protein?s amino acid sequence beginning at position 1804 and leads to a premature termination codon 2 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss o f function of the BRCA2 gene is an established disease mechanism in HBOC. In add ition, this variant was classified as pathogenic on Sept 8, 2016 by the ClinGen- approved ENIGMA expert panel (ClinVar SCV000300872.2). In summary, this variant meets criteria to be classified as pathogenic for HBOC in an autosomal dominant manner based on predicted impact to the protein and absence from controls.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000031544 SCV000296666 pathogenic Breast-ovarian cancer, familial 2 2015-05-29 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000219181 SCV000889067 pathogenic not provided 2015-05-29 criteria provided, single submitter clinical testing
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000044655 SCV000587766 pathogenic Hereditary breast and ovarian cancer syndrome 2014-01-31 no assertion criteria provided research
Sharing Clinical Reports Project (SCRP) RCV000031544 SCV000054149 pathogenic Breast-ovarian cancer, familial 2 2007-11-30 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.