Submissions for variant NM_001363711.2(DUOX2):c.1478del (p.His493fs)

gnomAD frequency: 0.00001  dbSNP: rs751410726

Total submissions: 2

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
GeneDx	RCV000478439	SCV000570147	likely pathogenic	not provided	2016-04-25	criteria provided, single submitter	clinical testing	The c.1478delA variant in the DUOX2 gene has not been reported previously as a pathogenic variant nor as a benign variant, to our knowledge. The c.1478delA variant causes a frameshift starting with codon Histidine 493, changes this amino acid to a Leucine residue, and creates a premature Stop codon at position 93 of the new reading frame, denoted p.His493LeufsX93. This variant is predicted to cause loss of normal protein function either through protein truncation or nonsense-mediated mRNA decay. The c.1478delA variant was not observed in approximately 6,500 individuals of European and African American ancestry in the NHLBI Exome Sequencing Project, indicating it is not a common benign variant in these populations. We interpret c.1478delA as a likely pathogenic variant.
Labcorp Genetics (formerly Invitae), Labcorp	RCV000478439	SCV002946612	pathogenic	not provided	2024-03-10	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.His493Leufs*93) in the DUOX2 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in DUOX2 are known to be pathogenic (PMID: 12110737, 18765513, 21565790, 24423310, 24735383). This variant is present in population databases (rs751410726, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with DUOX2-related conditions. ClinVar contains an entry for this variant (Variation ID: 421061). For these reasons, this variant has been classified as Pathogenic.