ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.3055C>G (p.Leu1019Val) (rs55638633)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 20
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000031398 SCV000244434 benign Breast-ovarian cancer, familial 2 2015-08-10 reviewed by expert panel curation IARC class based on posterior probability from multifactorial likelihood analysis, thresholds for class as per Plon et al. 2008 (PMID: 18951446). Class 1 based on posterior probability = 0.00000000714
Invitae RCV001079288 SCV000072121 benign Hereditary breast and ovarian cancer syndrome 2020-12-07 criteria provided, single submitter clinical testing
GeneDx RCV000755878 SCV000210585 likely benign not provided 2021-02-09 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 20104584, 12474142, 25637381, 21990134, 12845657, 21671020, 24323938, 23231788, 27376475, 21520273, 26332594, 17924331, 28283652, 30995915, 32444794, 32426482, 31851867, 31131967)
Ambry Genetics RCV000162553 SCV000212963 benign Hereditary cancer-predisposing syndrome 2014-11-19 criteria provided, single submitter clinical testing This alteration is classified as benign based on a combination of the following: population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Laboratory for Molecular Medicine, Partners HealthCare Personalized Medicine RCV000044108 SCV000538473 likely benign not specified 2016-03-28 criteria provided, single submitter clinical testing Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: All publications in HGMD list as non-pathogenic; ExAC: 16/66172 European chromosomes
Color Health, Inc RCV000162553 SCV000683523 likely benign Hereditary cancer-predisposing syndrome 2015-03-12 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000031398 SCV000743281 likely benign Breast-ovarian cancer, familial 2 2015-05-26 criteria provided, single submitter clinical testing
Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center RCV000031398 SCV000744435 benign Breast-ovarian cancer, familial 2 2015-09-21 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000162553 SCV000747809 likely benign Hereditary cancer-predisposing syndrome 2018-01-16 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283596 SCV000883521 benign none provided 2019-10-30 criteria provided, single submitter clinical testing
CHEO Genetics Diagnostic Laboratory,Children's Hospital of Eastern Ontario RCV000769690 SCV000901104 likely benign Breast and/or ovarian cancer 2016-12-29 criteria provided, single submitter clinical testing
Mendelics RCV000031398 SCV001139055 likely benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
CeGaT Praxis fuer Humangenetik Tuebingen RCV000755878 SCV001148979 likely benign not provided 2019-05-01 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001642296 SCV001854745 benign Breast-ovarian cancer, familial 2; Breast-ovarian cancer, familial 1; Hereditary breast and ovarian cancer syndrome 2020-01-20 criteria provided, single submitter curation
Sharing Clinical Reports Project (SCRP) RCV000031398 SCV000054003 benign Breast-ovarian cancer, familial 2 2008-06-07 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000031398 SCV000146160 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
CSER _CC_NCGL, University of Washington RCV000148419 SCV000190118 likely benign Breast neoplasm 2014-06-01 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV001353411 SCV000591845 benign Malignant tumor of breast no assertion criteria provided clinical testing The BRCA2 p.Leu1019Val variant was identified in 4 of 5690 proband chromosomes (frequency: 0.001) from individuals with breast or prostate cancer (Balia 2011 21671020, Capanu 2011, DeSanjose 2003, Edwards 2003). The variant was listed in dbSNP (ID: rs55638633) “With untested allele”, with one variant allele identified in the 1000 Genomes Project (frequency: 0.0005), and was identified in of 8590 European American alleles in the NHLBI Exome Sequencing Project (Exome Variant Server). However, this low number of observations and frequency is not substantive enough to determine the prevalence of this variant in the general population. The variant was also identified in HGMD, LOVD, the BIC database (22X with unknown clinical importance), and UMD (11X as a neutral variant). In UMD, the variant was identified in co-occurrence with two different pathogenic BRCA2 mutations and two different pathogenic BRCA1 mutations, increasing the likelihood that the p.Leu1019Val variant does not have clinical significance. The p.Leu1019 residue is conserved in mammals but not in lower organisms, and computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) do not suggest a high likelihood of impact to the protein. This information is not very predictive of pathogenicity. One functional assay found that expression of the variant did not increase spontaneous recombination in human cells, in a manner similar to expression of wild-type BRCA2 (Balia 2011). A yeast-based assay found that the variant demonstrated similar to wild-type homologous recombination (Spugnesi 2013). Three in silico models predicted the variant to be non-pathogenic or of no clinical significance (Capanu 2011, Easton 2007, Lindor 2012 21990134). In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.
Clinical Genetics Laboratory, Department of Pathology,Netherlands Cancer Institute RCV000044108 SCV001905814 benign not specified no assertion criteria provided clinical testing
Human Genetics - Radboudumc,Radboudumc RCV000044108 SCV001957586 benign not specified 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.