ClinVar Miner

Submissions for variant NM_001271.4(CHD2):c.361C>T (p.Arg121Ter)

dbSNP: rs397514740
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Total submissions: 4
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Center for Genomics, Ann and Robert H. Lurie Children's Hospital of Chicago RCV000054509 SCV000898594 pathogenic Developmental and epileptic encephalopathy 94 2021-11-11 criteria provided, single submitter clinical testing CHD2 NM_001271 exon 4 p.Arg121* (c.361C>T): This variant has been reported in the literature as de novo in 1 individual with epileptic encephalopathy (Carvill 2013 PMID:23708187). This variant is not present in large control databases. Evolutionary conservation and computational predictive tools for this variant are limited or unavailable. This variant is predicted to cause a stopgain at this codon, resulting in protein truncation or loss of allelic expression through nonsense-mediated mRNA decay. Loss of function has been suggested as a mechanism of disease for this gene (Carvill 2013 PMID:23708187). In summary, this variant is classified as likely pathogenic based on the data above (predicted impact to protein etc., presence as a de novo in literature).
GeneDx RCV003162428 SCV003915197 pathogenic not provided 2022-10-10 criteria provided, single submitter clinical testing Identified in a patient with epileptic encephalopathy in the published literature (PMID 29455050); Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 29455050, 24207121, 23708187)
Invitae RCV000054509 SCV004296608 pathogenic Developmental and epileptic encephalopathy 94 2023-01-31 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: 60712). This premature translational stop signal has been observed in individual(s) with epileptic encephalopathy (PMID: 23708187, 29455050). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg121*) 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).
OMIM RCV000054509 SCV000082987 pathogenic Developmental and epileptic encephalopathy 94 2013-07-01 no assertion criteria provided literature only

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