Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000799837 | SCV000939519 | pathogenic | Autoimmune lymphoproliferative syndrome type 1 | 2022-09-01 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 8 of the FAS gene. RNA analysis indicates that disruption of this splice site induces altered splicing and likely disrupts the C-terminus of the protein. This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Studies have shown that disruption of this splice site results in skipping of exon 8 and introduces a new termination codon (PMID: 10515860, 22237435). However the mRNA is not expected to undergo nonsense-mediated decay. ClinVar contains an entry for this variant (Variation ID: 645697). Disruption of this splice site has been observed in individuals with autoimmune lymphoproliferative syndrome (PMID: 10515860, 22237435). |