ClinVar Miner

Submissions for variant NM_001271.4(CHD2):c.1809+1G>A

dbSNP: rs1057520592
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV000426945 SCV000516192 pathogenic not provided 2017-01-04 criteria provided, single submitter clinical testing The c.1809+1G>A variant in the CHD2 gene has not been reported previously as a disease-causing variant nor as a benign variant, to our knowledge. This splice site variant destroys the canonical splice donor site in intron 15. It is predicted to cause abnormal gene splicing, either leading to an abnormal message that is subject to nonsense-mediated mRNA decay, or to an abnormal protein product if the message is used for protein translation. The c.1809+1G>A variant was not observed in approximately 6500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1809+1G>A as a pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp RCV001378270 SCV001575807 likely pathogenic Developmental and epileptic encephalopathy 94 2020-01-16 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site, but this prediction has not been confirmed by published transcriptional studies. This variant has not been reported in the literature in individuals with CHD2-related conditions. ClinVar contains an entry for this variant (Variation ID: 379377). This variant is not present in population databases (ExAC no frequency). This sequence change affects a donor splice site in intron 15 of the CHD2 gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. Donor and acceptor splice site variants typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in CHD2 are known to be pathogenic (PMID: 23708187, 24207121). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

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