Total submissions: 1
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV004018275 | SCV004847337 | likely pathogenic | Chronic mucocutaneous candidiasis | 2023-09-12 | criteria provided, single submitter | clinical testing | The c.599-1G>A variant in IL17RA has not been previously reported in individuals with IL17RA-associated diseases nor in large population studies. This variant occurs within the canonical splice site (+/- 1,2) and is predicted to cause altered splicing leading to an abnormal or absent protein. Biallelic loss of function variants in IL17RA have been observed in the homozygous state in consanguineous families with chronic mucocutaneous candidiasis (Puel 2011 PMID: 21350122, Levy 2016 PMID: 27930337) and IL17RA knock out mouse models have shown a decreased resistance to bacterial and fungal infections, recapitulating the human phenotype (Tan 2006 PMID: 16670328, Preibe 2008 PMID: 18802100, Kudva 2011 PMID: 21178015) and providing evidence that loss of function of this gene can cause disease. In summary, although additional studies are required to fully establish its clinical significance, this variant meets criteria to be classified as likely pathogenic for autosomal recessive chronic mucocutaneous candidiasis. ACMG/AMP Criteria applied: PVS1, PM2_Supporting. |