ClinVar Miner

Submissions for variant NM_001271.4(CHD2):c.1091A>G (p.Asn364Ser) (rs143043614)

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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 RCV000718993 SCV000849857 likely benign History of neurodevelopmental disorder 2017-05-31 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
GeneDx RCV000193134 SCV000721727 likely benign not specified 2017-08-15 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.
Genetic Services Laboratory, University of Chicago RCV000193134 SCV000247009 uncertain significance not specified 2015-02-25 criteria provided, single submitter clinical testing
Invitae RCV000688611 SCV000816231 uncertain significance Epileptic encephalopathy, childhood-onset 2018-08-15 criteria provided, single submitter clinical testing This sequence change replaces asparagine with serine at codon 364 of the CHD2 protein (p.Asn364Ser). The asparagine residue is highly conserved and there is a small physicochemical difference between asparagine and serine. This variant is present in population databases (rs143043614, 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: 210708). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The serine amino acid residue is found in multiple mammalian species, suggesting that this missense change does not adversely affect protein function. These predictions have not been confirmed by published functional studies and their clinical significance is uncertain. 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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