Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV000702363 | SCV000831215 | pathogenic | Developmental and epileptic encephalopathy, 8 | 2022-04-17 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. This sequence change affects a donor splice site in intron 4 of the ARHGEF9 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in ARHGEF9 are known to be pathogenic (PMID: 25678704, 26834553, 28589176). This variant is not present in population databases (gnomAD no frequency). Disruption of this splice site has been observed in individual(s) with early infantile epileptic encephalopathy (Invitae). In at least one individual the variant was observed to be de novo. ClinVar contains an entry for this variant (Variation ID: 579150). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. |
| Gene |
RCV002249418 | SCV002520109 | pathogenic | not provided | 2022-05-20 | criteria provided, single submitter | clinical testing | Canonical splice site variant expected to result in aberrant splicing, although in the absence of functional evidence the actual effect of this sequence change is unknown.; Not observed in large population cohorts (gnomAD); Has not been previously published as pathogenic or benign to our knowledge |