Total submissions: 5
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Ce |
RCV000487824 | SCV000575017 | benign | not provided | 2023-08-01 | criteria provided, single submitter | clinical testing | CHD2: BS1, BS2 |
| Gene |
RCV000487824 | SCV000709985 | pathogenic | not provided | 2017-10-26 | criteria provided, single submitter | clinical testing | The c.3734delA variant in the CHD2 gene has been reported previously in association with autism (Bi et al., 2012). The c.3734delA variant was also reported using alternate nomenclature (c.3725delA) in an individual with eyelid myoclonia with absences, autism, nephrolithiasis, migraines, and scoliosis (Galizia et al., 2015). The c.3734delA variant causes a frameshift starting with codon Lysine 1245, changes this amino acid to an Asparagine residue, and creates a premature Stop codon at position 4 of the new reading frame, denoted p.Lys1245AsnfsX4. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.3734delA variant is not observed in large population cohorts (Lek et al., 2016). We interpret c.3734delA as a pathogenic variant that is consistent with the reported developmental delay, autism, intellectual disability, ataxia, and abnormal EEG findings in this individual. |
| Ambry Genetics | RCV000719940 | SCV000850813 | pathogenic | History of neurodevelopmental disorder | 2020-10-08 | criteria provided, single submitter | clinical testing | The c.3734delA pathogenic mutation, located in coding exon 28 of the CHD2 gene, results from a deletion of one nucleotide at nucleotide position 3734, causing a translational frameshift with a predicted alternate stop codon (p.K1245Nfs*4). This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. As such, this alteration is interpreted as a disease-causing mutation. |
| Labcorp Genetics |
RCV001238241 | SCV001411040 | pathogenic | Developmental and epileptic encephalopathy 94 | 2022-02-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. ClinVar contains an entry for this variant (Variation ID: 425077). This premature translational stop signal has been observed in individual(s) with clinical features of CHD2-related conditions (PMID: 25783594). 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.Lys1245Asnfs*4) 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). |
| Laboratoire de Génétique Moléculaire, |
RCV001238241 | SCV003836731 | pathogenic | Developmental and epileptic encephalopathy 94 | 2022-06-27 | criteria provided, single submitter | clinical testing |