Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Diagnostic Laboratory, |
RCV001260659 | SCV001437751 | likely pathogenic | Intellectual disability | 2020-09-10 | criteria provided, single submitter | clinical testing | |
| Mendelics | RCV002246251 | SCV002518086 | uncertain significance | not specified | 2022-05-04 | criteria provided, single submitter | clinical testing | |
| Broad Center for Mendelian Genomics, |
RCV002537608 | SCV003761352 | uncertain significance | Developmental and epileptic encephalopathy 94 | 2023-01-25 | criteria provided, single submitter | curation | The heterozygous p.Lys1391AsnfsTer15 variant in CHD2 was identified by our study in one individual with epilepsy, global developmental delay, and agenesis of the corpus callosum. Trio exome analysis showed this variant to be de novo. The p.Lys1391AsnfsTer15 variant in CHD2 has not been previously reported in individuals with developmental and epileptic encephalopathy 94. This variant has also been reported in ClinVar (Variation ID: 981296) with conflicting interpretations of pathogenicity. Data from large population studies is insufficient to assess the frequency of this variant. This variant is predicted to cause a frameshift, which alters the protein’s amino acid sequence beginning at position 1391 and leads to a premature termination codon 15 amino acids downstream. This alteration is then predicted to lead to a truncated or absent protein. Heterozygous loss of function of the CHD2 is strongly associated to developmental and epileptic encephalopathy 94. In summary, while there is some suspicion for a pathogenic role, the clinical significance of this variant is uncertain. ACMG/AMP Criteria applied: PVS1_Strong, PS2_Supporting (Richards 2015). |
| Labcorp Genetics |
RCV002537608 | SCV005758267 | pathogenic | Developmental and epileptic encephalopathy 94 | 2024-07-06 | criteria provided, single submitter | clinical testing | This sequence change creates a premature translational stop signal (p.Lys1391Asnfs*15) in the CHD2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CHD2 are known to be pathogenic (PMID: 23708187, 24207121). 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 premature translational stop signal has been observed in individual(s) with clinical features of CHD2-related conditions (PMID: 34713950). ClinVar contains an entry for this variant (Variation ID: 981296). For these reasons, this variant has been classified as Pathogenic. |