Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Laboratory for Molecular Medicine, |
RCV000169658 | SCV000221186 | likely pathogenic | Thyroid dyshormonogenesis 6 | 2014-10-02 | criteria provided, single submitter | clinical testing | The c.3847+2T>C variant in DUOX2 has not been previously reported in the literature. This variant occurs in the invariant region (+/- 1,2) of the splice consensus sequence and is predicted to cause altered splicing leading to an abnormal or absent protein. In summary, although additional studies are required to fully establish its clinical significance, the c.3847+2T>C variant is likely pathogenic. |
Invitae | RCV001850409 | SCV002309108 | likely pathogenic | not provided | 2023-09-24 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 29 of the DUOX2 gene. It is expected to disrupt RNA splicing. Variants that disrupt the donor or acceptor splice site typically lead to a loss of protein function (PMID: 16199547), and loss-of-function variants in DUOX2 are known to be pathogenic (PMID: 12110737, 18765513, 21565790, 24423310, 24735383). This variant is present in population databases (rs199752932, gnomAD 0.01%). 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: 189228). 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 currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic. |