ClinVar Miner

Submissions for variant NM_001363711.2(DUOX2):c.2921G>A (p.Arg974His)

gnomAD frequency: 0.00003  dbSNP: rs778216481
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 3
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001911417 SCV002174481 uncertain significance not provided 2024-01-12 criteria provided, single submitter clinical testing This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 974 of the DUOX2 protein (p.Arg974His). This variant also falls at the last nucleotide of exon 22, which is part of the consensus splice site for this exon. This variant is present in population databases (rs778216481, gnomAD 0.1%). This missense change has been observed in individual(s) with congenital hypothyroidism (PMID: 29650690, 32425884, 33631011, 34539567). In at least one individual the data is consistent with being in trans (on the opposite chromosome) from a pathogenic variant. ClinVar contains an entry for this variant (Variation ID: 1400637). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. Variants that disrupt the consensus splice site are a relatively common cause of aberrant splicing (PMID: 17576681, 9536098). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.
Fulgent Genetics, Fulgent Genetics RCV002490196 SCV002791661 uncertain significance Thyroid dyshormonogenesis 6 2022-04-21 criteria provided, single submitter clinical testing
GeneDx RCV001911417 SCV005328234 uncertain significance not provided 2023-08-30 criteria provided, single submitter clinical testing Identified in unrelated individuals with congenital hypothyroidism who were also heterozygous for other variants in DUOX2; the phase of these variants was not reported (Sun F et al., 2018); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; In silico analysis supports that this missense variant does not alter protein structure/function; This variant is associated with the following publications: (PMID: 17576681, 33631011, 34539567, 33644218, 32425884, 29650690)

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. Neither the University of Utah nor the National Institutes of Health independently verfies the submitted information. If you have questions about the information contained on this website, please see a health care professional.