Total submissions: 4
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Knight Diagnostic Laboratories, |
RCV000454358 | SCV000538015 | likely pathogenic | Joubert syndrome 5 | 2016-03-30 | criteria provided, single submitter | clinical testing | The c.6818+1_6818+2insGG splice variant in the CEP290 gene has not been previously reported in published literature and is absent from the population databases (ESP; 1000 Genomes; ExAC). Splice-site, nonsense, and frameshift variants have been described in the CEP290 gene in several affected individuals (including nonsense and frameshift variants downstream of this splice variant) and thus, loss of function is a known mechanism of disease. In silico splicing algorithms predict this variant will cause altered splicing (Human Splice Finder = Broken WT Donor Site, New Donor Site). Therefore, this collective evidence supports the classification of the c.6818+1_6818+2insGG as a Likely Pathogenic variant for Joubert Syndrome and Related Disorders. Because this gene is expressed in blood cells, RNA-splicing studies can be performed to validate this classification (see recommendation). |
| Labcorp Genetics |
RCV000813873 | SCV000954254 | likely pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2023-07-28 | 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: 402224). This variant has not been reported in the literature in individuals affected with CEP290-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change affects a splice site in intron 49 of the CEP290 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 CEP290 are known to be pathogenic (PMID: 16909394, 17345604, 20690115). |
| Baylor Genetics | RCV003470389 | SCV004216691 | likely pathogenic | Bardet-Biedl syndrome 14 | 2023-03-05 | criteria provided, single submitter | clinical testing | |
| Fulgent Genetics, |
RCV005004159 | SCV005630371 | likely pathogenic | Leber congenital amaurosis 10; Meckel syndrome, type 4; Senior-Loken syndrome 6; Joubert syndrome 5; Bardet-Biedl syndrome 14 | 2024-06-20 | criteria provided, single submitter | clinical testing |