ClinVar Miner

Submissions for variant NM_001271.4(CHD2):c.4278+5T>C (rs202174434)

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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Ambry Genetics RCV000720423 SCV000851300 likely benign History of neurodevelopmental disorder 2018-02-21 criteria provided, single submitter clinical testing Lines of evidence used in support of classification: In silico models in agreement (benign),Subpopulation frequency in support of benign classification
CeGaT Praxis fuer Humangenetik Tuebingen RCV000658726 SCV000780513 likely benign not provided 2018-02-28 criteria provided, single submitter clinical testing
GeneDx RCV000426078 SCV000523574 likely benign not specified 2017-08-31 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.
Invitae RCV000651641 SCV000773495 uncertain significance Epileptic encephalopathy, childhood-onset 2018-12-13 criteria provided, single submitter clinical testing This sequence change falls in intron 33 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 present in population databases (rs202174434, ExAC 0.04%), and has an allele count higher than expected for a pathogenic variant (PMID: 28166811). This variant has not been reported in the literature in individuals with CHD2-related disease. ClinVar contains an entry for this variant (Variation ID: 383247). 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 is not likely to affect RNA splicing, 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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