Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV001040773 | SCV001204362 | likely pathogenic | Immunodeficiency 67 | 2021-11-20 | criteria provided, single submitter | clinical testing | ClinVar contains an entry for this variant (Variation ID: 3842). This variant has been observed in individual(s) with IRAK-4 deficiency (PMID: 16950813, 21057262). In at least one individual the data is consistent with the variant being in trans (on the opposite chromosome) from a pathogenic variant. This variant is not present in population databases (gnomAD no frequency). This sequence change falls in intron 10 of the IRAK4 gene. It does not directly change the encoded amino acid sequence of the IRAK4 protein. RNA analysis indicates that this variant induces altered splicing and may result in an absent or disrupted protein product. Studies have shown that this variant results in retention of an intronic fragment and introduces a premature termination codon (PMID: 16950813). The resulting mRNA is expected to undergo nonsense-mediated decay. In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |
OMIM | RCV001815160 | SCV000024212 | pathogenic | Invasive pneumococcal disease, recurrent isolated | 2007-01-01 | no assertion criteria provided | literature only |