Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002515602 | SCV003439650 | pathogenic | not provided | 2023-03-04 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 225524). For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 5 and introduces a premature termination codon (PMID: 26216346). The resulting mRNA is expected to undergo nonsense-mediated decay. Disruption of this splice site has been observed in individual(s) with immunodeficiency-centromeric instability-facial anomalies syndrome (PMID: 26216346). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs140316223, gnomAD 0.002%). This sequence change affects a donor splice site in intron 5 of the HELLS gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. |
OMIM | RCV000210918 | SCV000267577 | pathogenic | Immunodeficiency-centromeric instability-facial anomalies syndrome 4 | 2016-04-21 | no assertion criteria provided | literature only |