Submissions for variant NM_001111.5(ADAR):c.3286C>T (p.Arg1096Ter)

dbSNP: rs769148365

Total submissions: 6

Submitter	RCV	SCV	Clinical significance	Condition	Last evaluated	Review status	Method	Comment
Ambry Genetics	RCV001266911	SCV001445091	pathogenic	Inborn genetic diseases	2020-03-04	criteria provided, single submitter	clinical testing	The alteration results in a premature stop codon: The c.3286C>T (p.R1096*) alteration, located in coding exon 13 of the ADAR gene, results from a C to T substitution at nucleotide position 3286. This changes the amino acid from an arginine (R) to a stop codon at amino acid position 1096. This alteration is expected to result in loss of function by premature protein truncation or nonsense-mediated mRNA decay. The alteration has been observed in individuals with autosomal dominant dyschromatosis symmetrica hereditaria: This alteration has been reported in multiple patients with autosomal dominant dyschromatosis symmetrica hereditaria (Zhang, 2004; Kobayashi, 2018; Tang, 2018). Based on the available evidence, this alteration is classified as pathogenic.
Institute of Medical Genetics and Applied Genomics, University Hospital Tübingen	RCV001268344	SCV001447201	likely pathogenic	not provided	2020-10-23	criteria provided, single submitter	clinical testing
Baylor Genetics	RCV001332834	SCV001525261	pathogenic	Aicardi-Goutieres syndrome 6	2020-02-24	criteria provided, single submitter	clinical testing	This variant was determined to be pathogenic according to ACMG Guidelines, 2015 [PMID:25741868].
GeneDx	RCV001268344	SCV003926172	pathogenic	not provided	2022-11-17	criteria provided, single submitter	clinical testing	Nonsense variant predicted to result in protein truncation or nonsense mediated decay in a gene for which loss of function is a known mechanism of disease; Not observed at significant frequency in large population cohorts (gnomAD); This variant is associated with the following publications: (PMID: 25525159, 16086746, 32593192, 18243666, 22974014, 23315877, 15724015, 29185800, 15146470, 20186421, 17225010, 20430589, 29915444)
Genome-Nilou Lab	RCV001332834	SCV004050326	likely pathogenic	Aicardi-Goutieres syndrome 6	2023-04-11	criteria provided, single submitter	clinical testing
Invitae	RCV003770392	SCV004569133	pathogenic	Symmetrical dyschromatosis of extremities; Aicardi-Goutieres syndrome 6	2023-11-18	criteria provided, single submitter	clinical testing	This sequence change creates a premature translational stop signal (p.Arg1096*) 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). The frequency data for this variant in the population databases is considered unreliable, as metrics indicate poor data quality at this position in the gnomAD database. This premature translational stop signal has been observed in individual(s) with autosomal dominant dyschromatosis symmetrica hereditaria (PMID: 15146470, 29915444). It has also been observed to segregate with disease in related individuals. ClinVar contains an entry for this variant (Variation ID: 985814). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. For these reasons, this variant has been classified as Pathogenic.