Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Invitae | RCV002512922 | SCV003441593 | pathogenic | not provided | 2022-09-21 | criteria provided, single submitter | clinical testing | Disruption of this splice site has been observed in individual(s) with Dubin-Johnson syndrome (PMID: 9878557, 15870973, 29499989). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. This variant is present in population databases (rs387906396, gnomAD 0.02%). This sequence change affects a donor splice site in intron 15 of the ABCC2 gene. RNA analysis indicates that disruption of this splice site induces altered splicing and may result in an absent or disrupted protein product. ClinVar contains an entry for this variant (Variation ID: 8417). For these reasons, this variant has been classified as Pathogenic. Studies have shown that disruption of this splice site results in skipping of exon 15 and introduces a premature termination codon (PMID: 9878557). The resulting mRNA is expected to undergo nonsense-mediated decay. |
OMIM | RCV000008928 | SCV000029138 | pathogenic | Dubin-Johnson syndrome | 1998-12-18 | no assertion criteria provided | literature only |