Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV000819382 | SCV000960037 | pathogenic | Familial aplasia of the vermis | 2023-08-04 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as 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: 661866). Disruption of this splice site has been observed in individual(s) with features of Joubert syndrome (Invitae). This variant is present in population databases (rs187245292, gnomAD 0.008%). This sequence change affects a donor splice site in intron 17 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). |
| Ce |
RCV000998688 | SCV001154889 | pathogenic | not provided | 2022-08-01 | criteria provided, single submitter | clinical testing | |
| Women's Health and Genetics/Laboratory Corporation of America, |
RCV004768701 | SCV005381595 | likely pathogenic | Joubert syndrome and related disorders | 2024-08-02 | criteria provided, single submitter | clinical testing | Variant summary: AHI1 c.2492+1G>A is located in a canonical splice-site and is predicted to affect mRNA splicing resulting in a significantly altered protein due to either exon skipping, shortening, or inclusion of intronic material. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing and loss of AHI1 function. Several computational tools predict a significant impact on normal splicing: Three predict the variant abolishes a 5' splicing donor site. However, these predictions have yet to be confirmed by functional studies. The variant allele was found at a frequency of 9.9e-06 in 202156 control chromosomes. c.2492+1G>A has been reported in the literature in individuals affected with Joubert Syndrome And Related Disorders (Romero_2022). These data do not allow any conclusion about variant significance. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. The following publication have been ascertained in the context of this evaluation (PMID: 35087072). ClinVar contains an entry for this variant (Variation ID: 661866). Based on the evidence outlined above, the variant was classified as likely pathogenic. |
| Fulgent Genetics, |
RCV005036211 | SCV005668970 | likely pathogenic | Joubert syndrome 3 | 2024-06-07 | criteria provided, single submitter | clinical testing |