ClinVar Miner

Submissions for variant NM_002485.5(NBN):c.517A>G (p.Lys173Glu)

dbSNP: rs1563574056
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Mendelics RCV000709063 SCV000838313 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2018-07-02 criteria provided, single submitter clinical testing
Women's Health and Genetics/Laboratory Corporation of America, LabCorp RCV000781641 SCV000919852 uncertain significance not specified 2018-08-17 criteria provided, single submitter clinical testing Variant summary: NBN c.517A>G (p.Lys173Glu) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a damaging effect of the variant on protein function. The variant was absent in 121246 control chromosomes. The available data on variant occurrences in the general population are insufficient to allow any conclusion about variant significance. To our knowledge, no occurrence of c.517A>G in individuals affected with Nijmegen Breakage Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014. Based on the evidence outlined above, the variant was classified as uncertain significance.
Invitae RCV000709063 SCV001201338 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2023-12-02 criteria provided, single submitter clinical testing This sequence change replaces lysine, which is basic and polar, with glutamic acid, which is acidic and polar, at codon 173 of the NBN protein (p.Lys173Glu). This variant is not present in population databases (gnomAD no frequency). This missense change has been observed in individual(s) with breast cancer (PMID: 35264596). ClinVar contains an entry for this variant (Variation ID: 584729). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be disruptive. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Genome-Nilou Lab RCV000709063 SCV002045188 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2021-11-07 criteria provided, single submitter clinical testing

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