ClinVar Miner

Submissions for variant NM_001170629.2(CHD8):c.5483G>A (p.Arg1828His)

gnomAD frequency: 0.00022  dbSNP: rs199908540
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
GeneDx RCV001556581 SCV001778190 likely benign not provided 2021-04-22 criteria provided, single submitter clinical testing
CeGaT Center for Human Genetics Tuebingen RCV001556581 SCV002063113 likely benign not provided 2024-10-01 criteria provided, single submitter clinical testing CHD8: PP2, BS1
Ambry Genetics RCV002343731 SCV002652683 likely benign Inborn genetic diseases 2019-01-25 criteria provided, single submitter clinical testing This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity.
Labcorp Genetics (formerly Invitae), Labcorp RCV001556581 SCV003023680 uncertain significance not provided 2024-08-11 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 1828 of the CHD8 protein (p.Arg1828His). This variant is present in population databases (rs199908540, gnomAD 0.04%), and has an allele count higher than expected for a pathogenic variant. This missense change has been observed in individual(s) with neurodevelopmental disorder (PMID: 33004838). This variant is also known as c.5507G>A (p.Arg1836His). ClinVar contains an entry for this variant (Variation ID: 1193997). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CHD8 protein function with a negative predictive value of 80%. 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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