Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Illumina Laboratory Services, |
RCV000778639 | SCV000914965 | likely pathogenic | Inflammatory bowel disease 25 | 2018-02-20 | criteria provided, single submitter | clinical testing | The IL10RB c.611G>A (p.Trp204Ter) variant is a stop-gained variant that is predicted to result in premature termination of the protein. This variant has been reported in two studies and is found in three individuals with early-onset severe inflammatory bowel disease. This variant was found in a homozygous state in one proband and in a compound heterozygous state in two probands (Kotlarz et al. 2012; Shouval et al. 2016). One of the compound heterozygous individuals, who had a history of infantile IBD, also presented with large B-cell lymphoma (Shouval et al. 2016). Control data are unavailable for the p.Trp204Ter variant which is reported at a frequency of 0.000116 in the East Asian population of the Genome Aggregation Database, but this is based on two alleles in a region of good sequence coverage so the variant is presumed to be rare. Based on the evidence and the potential impact of stop-gained variants, the p.Trp204Ter variant is classified as likely pathogenic for inflammatory bowel disease. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population. |
| Labcorp Genetics |
RCV000778639 | SCV002232049 | pathogenic | Inflammatory bowel disease 25 | 2023-02-22 | criteria provided, single submitter | clinical testing | For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 631881). This premature translational stop signal has been observed in individuals with very early onset inflammatory bowel disease (PMID: 22549091, 27336593). This variant is present in population databases (no rsID available, gnomAD 0.01%). This sequence change creates a premature translational stop signal (p.Trp204*) in the IL10RB gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in IL10RB are known to be pathogenic (PMID: 22549091). |