Total submissions: 3
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
UW Hindbrain Malformation Research Program, |
RCV000201568 | SCV000256260 | pathogenic | Joubert syndrome 3 | 2015-02-23 | criteria provided, single submitter | research | |
Labcorp Genetics |
RCV001064139 | SCV001229020 | pathogenic | Familial aplasia of the vermis | 2023-10-06 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 11 of the AHI1 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 AHI1 are known to be pathogenic (PMID: 15322546, 16453322, 28442542, 29186038). This variant is present in population databases (no rsID available, gnomAD 0.003%). Disruption of this splice site has been observed in individuals with clinical features of Joubert syndrome (PMID: 16453322; Invitae). ClinVar contains an entry for this variant (Variation ID: 217535). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic. |
Gene |
RCV002277553 | SCV002567657 | likely pathogenic | not provided | 2022-02-17 | criteria provided, single submitter | clinical testing | Observed in a patient with Joubert syndrome who also harbored a second AHI1 variant; however segregation studies were not reported (Bachmann-Gagescu et al., 2015); 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 significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 33004012, 25525159, 16453322, 26092869) |