Total submissions: 3
| Submitter | RCV | SCV | Clinical significance | Condition | Last evaluated | Review status | Method | Comment |
|---|---|---|---|---|---|---|---|---|
| Counsyl | RCV000672259 | SCV000797350 | likely pathogenic | Polyglandular autoimmune syndrome, type 1 | 2018-01-23 | criteria provided, single submitter | clinical testing | |
| Labcorp Genetics |
RCV000672259 | SCV000961151 | likely pathogenic | Polyglandular autoimmune syndrome, type 1 | 2024-01-08 | criteria provided, single submitter | clinical testing | This sequence change affects a donor splice site in intron 5 of the AIRE 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 AIRE are known to be pathogenic (PMID: 11524731, 26141571). This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with AIRE-related conditions. ClinVar contains an entry for this variant (Variation ID: 556272). 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. |
| Neuberg Centre For Genomic Medicine, |
RCV000672259 | SCV004046902 | likely pathogenic | Polyglandular autoimmune syndrome, type 1 | criteria provided, single submitter | clinical testing | The splice site this sequence change affects a donor splice site in intron 5 of the AIRE gene. It is expected to disrupt RNA splicing and likely results in an absent or disrupted protein product. This variant has been reported previously in homozygous and compound heterozygous state. The variant is novel (not in any individuals) in 1000 Genomes and in gnomAD. This variant has been reported to the ClinVar database as Likely pathogenic. Donor and acceptor splice site variants typically lead to a loss of protein function (Baralle D et al), and loss-of-function variants in AIRE are known to be pathogenic (Kisand K et al). The nucleotide change in AIRE is predicted as conserved by GERP++ and PhyloP across 100 vertebrates. The variant is novel (not in any individuals) in gnomAD Exomes and 1000 Genomes. For these reasons, this variant has been classified as Likely Pathogenic. In the absence of another reportable variant the molecular diagnosis is not confirmed. |