Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000484093 | SCV000569934 | uncertain significance | not provided | 2016-04-12 | criteria provided, single submitter | clinical testing | A variant of uncertain significance has been identified in the CHD2 gene. The R223G variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. It was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. The R223G variant is a non-conservative amino acid substitution, which is likely to impact secondary protein structure as these residues differ in polarity, charge, size and/or other properties. This substitution occurs at a position that is conserved across species and in silico analysis predicts this variant is probably damaging to the protein structure/function. However, missense variants in nearby residues have not been reported in the Human Gene Mutation Database in association with CHD2-related disease (Stenson et al., 2014). Therefore, based on the currently available information, it is unclear whether this variant is a pathogenic variant or a rare benign variant. |
Ambry Genetics | RCV002367635 | SCV002663323 | uncertain significance | Inborn genetic diseases | 2018-09-29 | criteria provided, single submitter | clinical testing | The p.R223G variant (also known as c.667C>G), located in coding exon 6 of the CHD2 gene, results from a C to G substitution at nucleotide position 667. The arginine at codon 223 is replaced by glycine, an amino acid with dissimilar properties. This amino acid position is highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. |