Total submissions: 3
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- |
RCV003338692 | SCV004050346 | pathogenic | Aicardi-Goutieres syndrome 6 | 2023-04-11 | criteria provided, single submitter | clinical testing |