ClinVar Miner

Submissions for variant NM_001271.4(CHD2):c.2505+4A>G (rs767309501)

Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 2
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000486886 SCV000571360 uncertain significance not provided 2016-08-22 criteria provided, single submitter clinical testing A variant of uncertain significance has been identified in the CHD2 gene. The c.2505+4 A>G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. The c.2505+4 A>G variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). This substitution occurs at a position that is conserved across species. However, several in-silico splice prediction models predict that c.2505+4 A>G does not impact gene splicing. 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 RCV000686058 SCV000813561 uncertain significance Epileptic encephalopathy, childhood-onset 2018-03-20 criteria provided, single submitter clinical testing This sequence change falls in intron 19 of the CHD2 gene. It does not directly change the encoded amino acid sequence of the CHD2 protein, but it affects a nucleotide within the consensus splice site of the intron. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with CHD2-related disease. ClinVar contains an entry for this variant (Variation ID: 422004). Nucleotide substitutions within the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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.

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.