ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1222A>G (p.Lys408Glu) (rs34120922)

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Total submissions: 10
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories RCV000588672 SCV000885819 likely benign not provided 2017-08-15 criteria provided, single submitter clinical testing This variant has not been reported in association with primary immunodeficiency in medical literature or in gene specific variation databases. This variant is listed in the genome Aggregation Database (gnomAD) with an African population frequency of 0.9 percent (identified on 221 out of 24,028 chromosomes). The lysine at position 408 is weakly conserved (Alamut v.2.9.0) and computational analyses of the effects of the p.Lys408Glu variant on protein structure and function indicate a neutral effect (SIFT: tolerated, MutationTaster: polymorphism, PolyPhen-2: benign). Based on these observations, the p.Lys408Glu variant is likely to be benign.
Ambry Genetics RCV000115778 SCV000186613 likely benign Hereditary cancer-predisposing syndrome 2017-09-18 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Subpopulation frequency in support of benign classification,In silico models in agreement (benign)
Color RCV000115778 SCV000537498 likely benign Hereditary cancer-predisposing syndrome 2014-12-16 criteria provided, single submitter clinical testing
Counsyl RCV000119194 SCV000799488 likely benign Microcephaly, normal intelligence and immunodeficiency 2018-04-19 criteria provided, single submitter clinical testing
EGL Genetic Diagnostics,Eurofins Clinical Diagnostics RCV000200989 SCV000859935 likely benign not specified 2018-03-13 criteria provided, single submitter clinical testing
GeneDx RCV000200989 SCV000149687 likely benign not specified 2017-12-14 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.
Integrated Genetics/Laboratory Corporation of America RCV000588672 SCV000697940 likely benign not provided 2016-09-09 criteria provided, single submitter clinical testing Variant summary: The NBN c.1222A>G (p.Lys408Glu) variant involves the alteration of a non-conserved nucleotide. 5/5 in silico tools predict a benign outcome for this variant. This variant was found in 113/128570 control chromosomes, predominantly observed in the African subpopulation at a frequency of 0.0101923 (106/10400). This frequency is about 4 times the estimated maximal expected allele frequency of a pathogenic NBN variant (0.0025), suggesting this is likely a benign polymorphism found primarily in the populations of African origin. This variant has been reported in cancer patients without strong evidence of causality. In addition, multiple clinical diagnostic laboratories/reputable databases classified this variant as likely benign. Taken together, this variant is classified as likely benign.
Invitae RCV000119194 SCV000153931 benign Microcephaly, normal intelligence and immunodeficiency 2018-01-13 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000200989 SCV000601669 likely benign not specified 2017-03-24 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588672 SCV000889543 likely benign not provided 2018-04-28 criteria provided, single submitter clinical testing

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