ClinVar Miner


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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Invitae RCV001949465 SCV002245613 pathogenic Cernunnos-XLF deficiency 2021-09-02 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. This variant has not been reported in the literature in individuals affected with NHEJ1-related conditions. This variant is not present in population databases (ExAC no frequency). This sequence change inserts a large fragment of DNA, likely a transposable element, in exon 5 of the NHEJ1 gene (c.569_570ins?), causing a frameshift at codon 190 (p.Leu190Phefs). The exact size and sequence of the insertion cannot be determined by the current assay. However, the insertion is expected to result in an absent or disrupted protein product. For these reasons, this variant has been classified as Pathogenic. Retrotransposon insertions including LINE1 (L1), Alu, and SVA (SINE-VNTR-Alu) have been reported to be disease-causing through disruption of either a coding region or splice site (PMID: 19763152, 20307669, 22406018) and loss-of-function variants in NHEJ1 are known to be pathogenic (PMID: 16439204, 20597108).

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