ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1882G>A (p.Glu628Lys) (rs115321485)

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Total submissions: 12
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001084223 SCV000153825 benign Microcephaly, normal intelligence and immunodeficiency 2020-12-08 criteria provided, single submitter clinical testing
GeneDx RCV000212752 SCV000170642 benign not specified 2014-01-02 criteria provided, single submitter clinical testing This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease.
Ambry Genetics RCV000131006 SCV000185932 benign Hereditary cancer-predisposing syndrome 2014-12-02 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.
Center for Pediatric Genomic Medicine,Children's Mercy Hospital and Clinics RCV000224857 SCV000281644 likely benign not provided 2015-12-22 criteria provided, single submitter clinical testing Converted during submission to Likely benign.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000212752 SCV000601679 likely benign not specified 2017-03-10 criteria provided, single submitter clinical testing
Color Health, Inc RCV000131006 SCV000685740 benign Hereditary cancer-predisposing syndrome 2015-07-23 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000212752 SCV000697957 benign not specified 2021-04-24 criteria provided, single submitter clinical testing Variant summary: NBN c.1882G>A (p.Glu628Lys) results in a conservative amino acid change in the encoded protein sequence. Five of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00088 in 241282 control chromosomes, predominantly at a frequency of 0.012 within the African or African-American subpopulation in the gnomAD database. The observed variant frequency within African or African-American control individuals in the gnomAD database is approximately 96 fold of the estimated maximal expected allele frequency for a pathogenic variant in NBN causing Hereditary Breast And Ovarian Cancer Syndrome phenotype (0.00013), strongly suggesting that the variant is a benign polymorphism found primarily in populations of African or African-American origin. c.1882G>A has been reported in the literature in individuals who underwent testing for Hereditary Breast and Ovarian Cancer and/or Lynch Syndrome, without strong evidence for causality (examples- Haiman_2013, Yorczyk_2015, Yurgelun_2015, Tung_2015). These report(s) do not provide unequivocal conclusions about association of the variant with Hereditary Breast And Ovarian Cancer Syndrome. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Eight 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 benign (n=5)/likely benign (n=3). Based on the evidence outlined above, the variant was classified as benign.
PreventionGenetics,PreventionGenetics RCV000212752 SCV000806420 benign not specified 2016-11-22 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000224857 SCV000888329 benign not provided 2018-04-26 criteria provided, single submitter clinical testing
Illumina Clinical Services Laboratory,Illumina RCV001084223 SCV001324784 benign Microcephaly, normal intelligence and immunodeficiency 2017-04-28 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 rule this variant out of causing disease. Therefore, this variant is classified as benign.
ARUP Laboratories, Molecular Genetics and Genomics,ARUP Laboratories RCV001285232 SCV001471633 likely benign none provided 2019-08-22 criteria provided, single submitter clinical testing
Genome Diagnostics Laboratory, University Medical Center Utrecht RCV000224857 SCV001930305 likely benign not provided no assertion criteria provided clinical testing

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