ClinVar Miner

Submissions for variant NM_000059.4(BRCA2):c.5640T>G (p.Asn1880Lys) (rs11571657)

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Total submissions: 24
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Evidence-based Network for the Interpretation of Germline Mutant Alleles (ENIGMA) RCV000077358 SCV001161664 benign Breast-ovarian cancer, familial 2 2019-06-18 reviewed by expert panel curation Variant allele has low bioinformatic likelihood to encode a missense alteration affecting protein function (Missense prior probability 0.02; http://priors.hci.utah.edu/PRIORS/), AND low bioinformatic likelihood to alter mRNA splicing (splicing prior 0.02; http://priors.hci.utah.edu/PRIORS/), AND minor allele frequency 0.00909 (African), derived from gnomAD v2.1.1 non-cancer (2019-05-13).
Invitae RCV000044703 SCV000072716 benign Hereditary breast and ovarian cancer syndrome 2020-12-06 criteria provided, single submitter clinical testing
GeneDx RCV001703946 SCV000167373 benign not provided 2018-11-30 criteria provided, single submitter clinical testing This variant is associated with the following publications: (PMID: 21520273, 25637381, 11241844, 27884173, 26332594, 24728327, 11950811, 12624724, 9971877, 20104584, 19491284, 16030099, 22034289, 18724707, 12491487, 27741520)
Ambry Genetics RCV000129180 SCV000183915 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.
Counsyl RCV000077358 SCV000220345 benign Breast-ovarian cancer, familial 2 2014-05-23 criteria provided, single submitter literature only
EGL Genetic Diagnostics, Eurofins Clinical Diagnostics RCV000120348 SCV000225180 benign not specified 2014-12-04 criteria provided, single submitter clinical testing
Michigan Medical Genetics Laboratories,University of Michigan RCV000077358 SCV000267783 likely benign Breast-ovarian cancer, familial 2 2016-04-21 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV000301382 SCV000383721 likely benign Fanconi anemia, complementation group D1 2018-10-25 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Illumina Clinical Services Laboratory,Illumina RCV000077358 SCV000383722 likely benign Breast-ovarian cancer, familial 2 2018-10-25 criteria provided, single submitter clinical testing This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). Publications were found based on this search. The evidence from the literature, in combination with allele frequency data from public databases where available, was sufficient to determine this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign.
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000044703 SCV000494332 benign Hereditary breast and ovarian cancer syndrome 2014-04-18 criteria provided, single submitter clinical testing
Genetic Services Laboratory, University of Chicago RCV000120348 SCV000593717 benign not specified 2018-07-20 criteria provided, single submitter clinical testing
Institute for Biomarker Research, Medical Diagnostic Laboratories, L.L.C. RCV000129180 SCV000679718 likely benign Hereditary cancer-predisposing syndrome 2017-07-12 criteria provided, single submitter clinical testing
Color Health, Inc RCV000129180 SCV000683720 benign Hereditary cancer-predisposing syndrome 2016-05-24 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000120348 SCV000805728 benign not specified 2017-07-10 criteria provided, single submitter clinical testing
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001283467 SCV000883470 benign none provided 2020-01-03 criteria provided, single submitter clinical testing
Mendelics RCV000077358 SCV001139120 benign Breast-ovarian cancer, familial 2 2019-05-28 criteria provided, single submitter clinical testing
Research and Development, ARUP Laboratories RCV001646419 SCV001854848 likely 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
ITMI RCV000120348 SCV000084500 not provided not specified 2013-09-19 no assertion provided reference population
Sharing Clinical Reports Project (SCRP) RCV000077358 SCV000109155 benign Breast-ovarian cancer, familial 2 2008-08-01 no assertion criteria provided clinical testing
Breast Cancer Information Core (BIC) (BRCA2) RCV000077358 SCV000146650 uncertain significance Breast-ovarian cancer, familial 2 2002-05-29 no assertion criteria provided clinical testing
CSER _CC_NCGL, University of Washington RCV000148422 SCV000190121 likely benign Breast neoplasm 2014-06-01 no assertion criteria provided research
Research Molecular Genetics Laboratory,Women's College Hospital, University of Toronto RCV000120348 SCV000587783 benign not specified 2015-12-17 no assertion criteria provided research
Department of Pathology and Laboratory Medicine,Sinai Health System RCV000077358 SCV000591981 benign Breast-ovarian cancer, familial 2 no assertion criteria provided clinical testing The p.Asn1880Lys variant has been previously observed in 7/5248 (frequency: 0.001) proband chromosomes from individuals with a family history of breast and/or ovarian cancer (Borg 2010, Haffty 2009, Real 2002, Weitzel 2005). This individuals racial origin is reported to be of African American ancestry and of the individuals reported in the literature with the p.Asn1880Lys variant, 3 were reported of African American descent. In addition, in the Exome Variant Server this variant was not found in any of the 8,600 Caucasian control chromosomes, but was found in 41/4365 (frequency: 0.009) African American control chromosomes increasing the likelihood that this variant is a benign polymorphism in this population of origin. It should also be noted that this lab has sequenced the BRCA2 gene in a limited number of African American individuals such that the full spectrum of benign variation has not yet been defined for this population, and increasing the possibility that this may be a benign variant. Future analysis could reveal that the p.Asn1880Lys variant is common in this population and therefore unlikely to be of clinical significance. It is listed in dbSNP database as coming from a "clinical source" (ID#: rs11571657) with a global minor allele frequency (MAF) of 0.002 (1000 Genomes) further lending to a benign role for this variant. Finally, this residue is not conserved in mammals and computational analyses (PolyPhen, SIFT, AlignGVGD) do not suggest a high likelihood of impact to the protein, further leaning to a benign role for this variant. In summary, we cannot rule out the possibility that this variant may contribute to the phenotype in this individual, but based on the above information this variant is classified as benign.
Foulkes Cancer Genetics LDI, Lady Davis Institute for Medical Research RCV000735568 SCV000863706 pathogenic Breast and/or ovarian cancer 2012-05-08 no assertion criteria provided clinical testing

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