Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Labcorp Genetics |
RCV000693767 | SCV000821648 | likely pathogenic | Immunodeficiency, common variable, 10 | 2018-02-08 | criteria provided, single submitter | clinical testing | Studies have shown that processing of p100 into active p52 depends upon phosphorylation of two conserved serine residues at amino acids 866 and 870 (PMID: 16303288, 24140114). This suggests that this frameshift variant, which disrupts both of these residues, is likely to prevent appropriate p100 phosphorylation and processing. 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. This variant has not been reported in the literature in individuals with NFKB2-related disease. This variant is not present in population databases (ExAC no frequency). This sequence change results in a premature translational stop signal in the NFKB2 gene (p.Thr859Argfs*25). While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 42 amino acids of the NFKB2 protein. |