Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Invitae | RCV001989682 | SCV002282978 | likely pathogenic | Cortical dysplasia-focal epilepsy syndrome | 2023-01-02 | criteria provided, single submitter | clinical testing | In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely 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: 1494963). This variant has not been reported in the literature in individuals affected with CNTNAP2-related conditions. 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 affects an acceptor splice site in intron 22 of the CNTNAP2 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 CNTNAP2 are known to be pathogenic (PMID: 19896112, 21827697, 25045150, 26843181, 27439707). |
| Gene |
RCV002274246 | SCV002559750 | uncertain significance | not provided | 2022-02-04 | 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; Has not been previously published as pathogenic or benign to our knowledge |