ClinVar Miner

Submissions for variant NM_002485.4(NBN):c.1914+10G>A (rs577706448)

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Total submissions: 8
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000192466 SCV000170643 benign not specified 2014-02-25 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.
Genetic Services Laboratory,University of Chicago RCV000192466 SCV000248135 uncertain significance not specified 2014-12-05 criteria provided, single submitter clinical testing
Invitae RCV000232925 SCV000287459 benign Microcephaly, normal intelligence and immunodeficiency 2019-12-31 criteria provided, single submitter clinical testing
Color RCV000581136 SCV000685742 likely benign Hereditary cancer-predisposing syndrome 2015-04-29 criteria provided, single submitter clinical testing
Counsyl RCV000232925 SCV000794667 likely benign Microcephaly, normal intelligence and immunodeficiency 2017-10-11 criteria provided, single submitter clinical testing
PreventionGenetics,PreventionGenetics RCV000679456 SCV000806422 likely benign not provided 2017-03-10 criteria provided, single submitter clinical testing
Quest Diagnostics Nichols Institute San Juan Capistrano RCV000679456 SCV001134503 benign not provided 2019-03-19 criteria provided, single submitter clinical testing
Integrated Genetics/Laboratory Corporation of America RCV000192466 SCV001337976 likely benign not specified 2020-01-23 criteria provided, single submitter clinical testing Variant summary: NBN c.1914+10G>A alters a non-conserved nucleotide located close to a canonical splice site and therefore could affect mRNA splicing, leading to a significantly altered protein sequence. 4/4 computational tools predict no significant impact on normal splicing. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 0.00027 in 220710 control chromosomes in the gnomAD database, including 1 homozygote. This frequency is not significantly higher than expected for a pathogenic variant in NBN causing Nijmegen Breakage Syndrome (0.00027 vs 0.0025), allowing no conclusion about variant significance. To our knowledge, no occurrence of c.1914+10G>A in individuals affected with Nijmegen Breakage Syndrome and no experimental evidence demonstrating its impact on protein function have been reported. Five ClinVar submitters (evaluation after 2014) cite the variant as benign/likely benign. Based on the evidence outlined above, the variant was classified as likely benign.

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