ClinVar Miner

Submissions for variant NM_020661.4(AICDA):c.544-2A>G

gnomAD frequency: 0.00001  dbSNP: rs772388034
Minimum review status: Collection method:
Minimum conflict level:
ClinVar version:
Total submissions: 1
Download table as spreadsheet
Submitter RCV SCV Clinical significance Condition Last evaluated Review status Method Comment
Labcorp Genetics (formerly Invitae), Labcorp RCV001969612 SCV002266196 likely pathogenic Hyper-IgM syndrome type 2 2021-07-15 criteria provided, single submitter clinical testing This sequence change affects an acceptor splice site in intron 4 of the AICDA gene. While this variant is not anticipated to result in nonsense mediated decay, it likely alters RNA splicing and results in a disrupted protein product. 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. Nucleotide substitutions within 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. Experimental studies have shown that disruption of this splice site affects AICDA protein function (PMID: 12910268). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. This variant is also known as V5-2A>G. Disruption of this splice site has been observed in individuals with autosomal recessive hyper IgM syndrome (PMID: 14962793; Invitae). This variant is present in population databases (rs772388034, ExAC 0.006%).

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.