Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV000523555 | SCV000618437 | likely pathogenic | not provided | 2017-04-20 | criteria provided, single submitter | clinical testing | A variant that is likely pathogenic has been identified in the KCNQ2 gene. The c.1631+5 G>A variant has not been published as a pathogenic variant, nor has it been reported as a benign variant to our knowledge. Several in-silico splice prediction models predict that c.1631+5 G>A destroys the natural splice donor site in intron 14 and is expected to cause to abnormal gene splicing. However, in the absence of RNA/functional studies, the actual effect of this sequence change in this individual is unknown. The c.1631+5 G>A variant is not observed in large population cohorts (Lek et al., 2016; 1000 Genomes Consortium et al., 2015; Exome Variant Server). Therefore, this variant is likely pathogenic; however, the possibility that it is benign cannot be excluded. |
Invitae | RCV001853628 | SCV002317844 | uncertain significance | Early infantile epileptic encephalopathy with suppression bursts | 2022-11-22 | criteria provided, single submitter | clinical testing | This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). 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: 449951). This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 14 of the KCNQ2 gene. It does not directly change the encoded amino acid sequence of the KCNQ2 protein. It affects a nucleotide within the consensus splice site. |