Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Gene |
RCV001557279 | SCV001779011 | likely pathogenic | not provided | 2020-12-10 | criteria provided, single submitter | clinical testing | Has not been previously published as pathogenic or benign to our knowledge; 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 at a significant frequency in large population cohorts (Lek et al., 2016) |
Fulgent Genetics, |
RCV002501901 | SCV002810505 | likely pathogenic | Epilepsy, idiopathic generalized, susceptibility to, 11; Familial hyperaldosteronism type II; Leukoencephalopathy with mild cerebellar ataxia and white matter edema | 2024-03-04 | criteria provided, single submitter | clinical testing | |
Labcorp Genetics |
RCV001557279 | SCV003506618 | likely pathogenic | not provided | 2023-07-07 | criteria provided, single submitter | clinical testing | This variant is present in population databases (rs141074059, gnomAD 0.04%). 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: 1194517). This variant has not been reported in the literature in individuals affected with CLCN2-related conditions. This sequence change affects a donor splice site in intron 8 of the CLCN2 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 CLCN2 are known to be pathogenic (PMID: 23707145). |