Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Mendelics | RCV000989404 | SCV001139723 | pathogenic | Developmental and epileptic encephalopathy 94 | 2023-03-30 | criteria provided, single submitter | clinical testing | |
Invitae | RCV000989404 | SCV001583903 | pathogenic | Developmental and epileptic encephalopathy 94 | 2022-01-13 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 803141). This premature translational stop signal has been observed in individual(s) with early-onset epileptic encephalopathy (PMID: 31677157). In at least one individual the variant was observed to be de novo. 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 sequence change creates a premature translational stop signal (p.Tyr1246Ilefs*13) 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). |
Prevention |
RCV003973000 | SCV004798720 | likely pathogenic | CHD2-related condition | 2024-02-20 | criteria provided, single submitter | clinical testing | The CHD2 c.3734dupA variant is predicted to result in a frameshift and premature protein termination (p.Tyr1246Ilefs*13). This variant was reported to occur de novo in an individual with an epilepsy phenotype (Supplemental Table 1, Chen et al 2019. PubMed ID: 31677157). This variant is reported in 1.9% of alleles in individuals of Ashkenazi Jewish descent in gnomAD, however this variant is within a region of sequence complexity and thus population-based frequency reports based on short read next-generation sequencing technology are likely inaccurate. However, frameshift variants in CHD2 are expected to be pathogenic and therefore we interpret this variant as likely pathogenic. |