ClinVar Miner

Submissions for variant NM_021044.4(DHH):c.528C>A (p.Tyr176Ter)

dbSNP: rs1565573786
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Total submissions: 1
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Human Genetics Laboratory, Faculty of Medicine of Tunis RCV000714234 SCV000804755 pathogenic 46,XY sex reversal 7 criteria provided, single submitter research The p.Tyr176* is a novel DHH gene variant identified in a 46,XY CGD female patient. This variation is not listed in gnomAD browser database (http://gnomad.broadinstitute.org) or the Human Gene Mutations Database (HGMD) (http://www.hgmd.org/) or 1000 genomes project which likely reflects a novel mutation. It lies in the auto-catalytically processed and secreted DHh-N. It gives rise to a premature stop codon instead of tyrosine residue at amino acid position 176, leading to a truncated protein missing the last 23 amino acids of DHh-N as well as the entire DHh-C containing the determinants required for auto-processing of the precursor as well as all the essential residues fundamental for addition of a cholesterol moiety to the signaling peptide DHh-N. This mutation was found associated as a compound heterozygous mutation in DHh-C in a patient with CGD. The second mutation showed abolished auto-catalytic processing in vitro. Thus, the p.Tyr176* variant meets our criteria to be classified as autosomal recessive pathogenic.

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