Total submissions: 2
Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
---|---|---|---|---|---|---|---|---|
Rady Children's Institute for Genomic Medicine, |
RCV001265561 | SCV001443716 | likely pathogenic | Thyroid dyshormonogenesis 6 | 2019-09-24 | criteria provided, single submitter | clinical testing | This variant affects the canonical splice acceptor site of intron 30 of 33, and is therefore predicted to interfere with splicing and result in loss of normal protein function. This variant has not been previously reported in an affected individual or functionally characterized in the literature to our knowledge. It is present in the heterozygous state in the gnomAD population database at a frequency of 0.002% (5/246172) and thus is presumed to be rare. Multiple splice prediction tools suggest this variant is likely to interfere with normal splicing. Based on the available evidence, the c.4081-1G>A variant is classified as Likely Pathogenic. |
Invitae | RCV003558777 | SCV004296968 | likely pathogenic | not provided | 2023-12-15 | criteria provided, single submitter | clinical testing | This sequence change affects an acceptor splice site in intron 30 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 (rs549559724, gnomAD 0.004%). 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: 984928). 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. |