ClinVar Miner

Submissions for variant NM_001363711.2(DUOX2):c.1883del (p.Lys628fs)

dbSNP: rs200592893
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Total submissions: 2
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Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Illumina Laboratory Services, Illumina RCV000778438 SCV000914684 likely pathogenic Thyroid dyshormonogenesis 6 2017-07-26 criteria provided, single submitter clinical testing The DUOX2 c.1883delA (p.Lys628ArgfsTer11) variant results in a frameshift, and is predicted to result in premature termination of the protein. The p.Lys628ArgfsTer11 variant has been reported in two studies in which it is found in a compound heterozygous state with a second variant in five individuals, including four siblings, three of whom were diagnosed with transient congenital hypothyroidism and one who was diagnosed with transient hyperthyrotroinemia and mild learning disability. The unaffected mother of the four siblings was also a carrier of the p.Lys628ArgfsTer11 variant (Maruo et al. 2008; Maruo et al. 2016; Tan et al. 2016). The variant was absent from 100 Japanese control alleles and is reported at a frequency of 0.000318 in the East Asian population of the Genome Aggregation Database. Based on the evidence and the potential impact of frameshift variants, the p.Lys628ArgfsTer11 variant is classified as likely pathogenic for congenital hypothyroidism. This variant was observed by ICSL as part of a predisposition screen in an ostensibly healthy population.
Invitae RCV001856159 SCV002236716 pathogenic not provided 2024-01-29 criteria provided, single submitter clinical testing This sequence change creates a premature translational stop signal (p.Lys628Argfs*11) 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 (rs200592893, gnomAD 0.03%). This premature translational stop signal has been observed in individual(s) with congenital hypothyroidism (PMID: 18765513, 30022773, 32459320). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 631734). For these reasons, this variant has been classified as Pathogenic.

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