ClinVar Miner

Submissions for variant NM_001111.5(ADAR):c.2433_2434del (p.Ala813fs)

gnomAD frequency: 0.00001  dbSNP: rs779357448
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
Ambry Genetics RCV000622621 SCV000742077 pathogenic Inborn genetic diseases 2022-05-10 criteria provided, single submitter clinical testing The c.2433_2434delAG (p.A813Qfs*29) alteration, located in exon 7 (coding exon 7) of the ADAR gene, consists of a deletion of 2 nucleotides from position 2433 to 2434, causing a translational frameshift with a predicted alternate stop codon after 29 amino acids. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. Based on data from gnomAD, this alteration has an overall frequency of <0.01% (3/282806) total alleles studied. The highest observed frequency was 0.01% (1/19950) of East Asian alleles. This alteration has been previously reported in individuals with autosomal dominant dyschromatosis symmetrica hereditaria (DSH) (Liu, 2021; Lee, 2014; Tang, 2018; Zhang, 2004). Based on the available evidence, this alteration is classified as pathogenic.
Invitae RCV000694985 SCV000823458 pathogenic Symmetrical dyschromatosis of extremities; Aicardi-Goutieres syndrome 6 2023-08-17 criteria provided, single submitter clinical testing Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may create or strengthen a splice site. For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 521470). This premature translational stop signal has been observed in individual(s) with dyschromatosis symmetrica hereditaria (PMID: 15146470, 25468572, 29185800). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs779357448, gnomAD 0.007%). This sequence change creates a premature translational stop signal (p.Ala813Glnfs*29) in the ADAR gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in ADAR are known to be pathogenic (PMID: 22974014).
Genome-Nilou Lab RCV003338692 SCV004050346 pathogenic Aicardi-Goutieres syndrome 6 2023-04-11 criteria provided, single submitter clinical testing

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.