ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.207A>G (p.Lys69=) (rs754352569)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Color RCV000771592 SCV000904194 likely benign Hereditary cancer-predisposing syndrome 2018-08-28 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000588237 SCV000697960 uncertain significance not provided 2017-06-09 criteria provided, single submitter clinical testing Variant summary: The NBN c.207A>G (p.Lys69Lys) variant involves the alteration of a conserved nucleotide causing a synonymous change that 3/5 splice prediction tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. This variant was found in 3/121234 control chromosomes at a frequency of 0.0000247, which does not exceed the estimated maximal expected allele frequency of a pathogenic NBN variant (0.0025). The variant of interest has not, to our knowledge, been reported in affected individuals via publications and/or reputable databases/clinical diagnostic laboratories; nor evaluated for functional impact by in vivo/vitro studies. Taken together, this variant is classified as a "Variant of Uncertain Significance - Possibly Benign."
Invitae RCV000808156 SCV000948250 uncertain significance Microcephaly, normal intelligence and immunodeficiency 2018-08-10 criteria provided, single submitter clinical testing This sequence change affects codon 69 of the NBN mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the NBN protein. This variant is present in population databases (rs754352569, ExAC 0.02%). This variant has not been reported in the literature in individuals with NBN-related disease. ClinVar contains an entry for this variant (Variation ID: 439223). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site, but this prediction has not been confirmed by published transcriptional studies. 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.
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000507040 SCV000601682 uncertain significance not specified 2017-07-19 criteria provided, single submitter clinical testing

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