Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Genetic Services Laboratory, |
RCV000147012 | SCV000194352 | pathogenic | Lissencephaly due to LIS1 mutation | 2013-02-08 | criteria provided, single submitter | clinical testing | |
Invitae | RCV001857518 | SCV002111090 | pathogenic | not provided | 2023-07-14 | criteria provided, single submitter | clinical testing | Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. This variant disrupts a region of the PAFAH1B1 protein in which other variant(s) (p.His389Tyr) have been determined to be pathogenic (PMID: 19808989). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 159496). This variant has not been reported in the literature in individuals affected with PAFAH1B1-related conditions. This sequence change affects a donor splice site in intron 10 of the PAFAH1B1 gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. This variant is not present in population databases (gnomAD no frequency). |