ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1282A>G (p.Asn428Asp) (rs786202302)

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Total submissions: 5
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000165044 SCV000215743 uncertain significance Hereditary cancer-predisposing syndrome 2016-04-04 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: Insufficient or conflicting evidence,In silico models in agreement (benign),Rarity in general population databases (dbsnp, esp, 1000 genomes)
Invitae RCV000476294 SCV000553061 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2018-12-24 criteria provided, single submitter clinical testing This sequence change replaces asparagine with aspartic acid at codon 428 of the NBN protein (p.Asn428Asp). The asparagine residue is weakly conserved and there is a small physicochemical difference between asparagine and aspartic acid. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with NBN-related disease. ClinVar contains an entry for this variant (Variation ID: 185597). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The aspartic acid amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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.
Integrated Genetics/Laboratory Corporation of America RCV000588529 SCV000697943 uncertain significance not provided 2017-03-03 criteria provided, single submitter clinical testing Variant summary: The NBN c.1282A>G (p.Asn428Asp) variant involves the alteration of a non-conserved nucleotide, which 5/5 in silico tools predict a benign outcome, although these predictions have yet to be functionally observed. The variant of interest has not been observed in controls (ExAC, 1000 Gs, or ESP), nor has it been, to our knowledge, reported in affected individuals via publications. A clinical diagnostic laboratory cites the variant with a classification of "uncertain significance." Therefore, until additional information becomes available (ie, clinical and functional studies), the variant of interest has been classified as a "Variant of Uncertain Significance (VUS)."
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000588529 SCV000889545 uncertain significance not provided 2019-06-14 criteria provided, single submitter clinical testing
Color RCV000165044 SCV000909708 uncertain significance Hereditary cancer-predisposing syndrome 2018-07-29 criteria provided, single submitter clinical testing

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