Total submissions: 2
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Labcorp Genetics |
RCV001202440 | SCV001373552 | uncertain significance | Immunodeficiency 67 | 2022-07-06 | criteria provided, single submitter | clinical testing | This sequence change replaces glutamic acid, which is acidic and polar, with lysine, which is basic and polar, at codon 116 of the IRAK4 protein (p.Glu116Lys). This variant is present in population databases (rs62642475, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with IRAK4-related conditions. ClinVar contains an entry for this variant (Variation ID: 934104). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. |
| Neuberg Centre For Genomic Medicine, |
RCV001202440 | SCV005060963 | uncertain significance | Immunodeficiency 67 | criteria provided, single submitter | clinical testing | The missense c.346G>A (p.Glu116Lys) variant in IRAK4 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. This variant is reported with an allele frequency of 0.0004% in the gnomAD exomes database. This variant has been reported to the ClinVar database as Uncertain Significance. The amino acid change p.Glu116Lys in IRAK4 is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The amino acid Glu at position 116 is changed to a Lys changing protein sequence and it might alter its composition and physico-chemical properties. For these reasons, this variant has been classified as a Variant of Uncertain Significance (VUS). |