ClinVar Miner

Submissions for variant NM_003159.2(CDKL5):c.2520C>T (p.Arg840=) (rs1037569177)

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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000414329 SCV000492123 uncertain significance not provided 2016-11-28 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CDKL5 gene. The c.2520 C>T variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2520 C>T variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. This substitution occurs at a position that is not conserved. Several in-silico splice prediction models predict that c.2520 C>T may create a cryptic donor site in exon 18 and lead to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant.
Invitae RCV000819789 SCV000960470 uncertain significance Early infantile epileptic encephalopathy 2; Angelman syndrome-like 2018-11-03 criteria provided, single submitter clinical testing This sequence change affects codon 840 of the CDKL5 mRNA. It is a 'silent' change, meaning that it does not change the encoded amino acid sequence of the CDKL5 protein. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CDKL5-related disease. ClinVar contains an entry for this variant (Variation ID: 373525). 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.

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