Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV002894942 | SCV003245040 | pathogenic | Familial aplasia of the vermis; Meckel-Gruber syndrome; Nephronophthisis | 2022-05-24 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 24 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. Disruption of this splice site has been observed in individual(s) with Joubert syndrome and related disorders (PMID: 25097241, 32619255). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. 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. |
Baylor Genetics | RCV003465862 | SCV004216717 | likely pathogenic | Bardet-Biedl syndrome 14 | 2023-01-12 | criteria provided, single submitter | clinical testing |