Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Center for Genomics, |
RCV000768176 | SCV000898595 | uncertain significance | Developmental and epileptic encephalopathy 94 | 2021-03-30 | criteria provided, single submitter | clinical testing | CHD2 NM_001271.3 exon 7 p.Gln198His (c.594G>C): This variant has not been reported in the literature but is present in 10/17246 East Asian alleles in the Genome Aggregation Database (http://gnomad.broadinstitute.org/rs374064833). Evolutionary conservation and computational predictive tools for this variant are unclear. In summary, data on this variant is insufficient for disease classification. Therefore, the clinical significance of this variant is uncertain. |
| Labcorp Genetics |
RCV000768176 | SCV000947828 | uncertain significance | Developmental and epileptic encephalopathy 94 | 2023-11-27 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamine, which is neutral and polar, with histidine, which is basic and polar, at codon 198 of the CHD2 protein (p.Gln198His). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This missense change has been observed in individual(s) with autism and/or developmental delay (PMID: 30564305). ClinVar contains an entry for this variant (Variation ID: 626082). 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 CHD2 protein function with a negative predictive value of 95%. 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. |
| Ambry Genetics | RCV002536599 | SCV003684412 | likely benign | Inborn genetic diseases | 2021-07-10 | 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. |