rs762568334
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 1P and 1B. PP2BP4
The NM_001111.5(ADAR):c.2548C>T(p.Arg850Trp) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000018 in 1,613,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R850Q) has been classified as Uncertain significance.
Frequency
Consequence
NM_001111.5 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Uncertain_significance. Variant got 0 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
ADAR | NM_001111.5 | c.2548C>T | p.Arg850Trp | missense_variant | 8/15 | ENST00000368474.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
ADAR | ENST00000368474.9 | c.2548C>T | p.Arg850Trp | missense_variant | 8/15 | 1 | NM_001111.5 | P3 |
Frequencies
GnomAD3 genomes ? AF: 0.00000658 AC: 1AN: 152036Hom.: 0 Cov.: 31
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251228Hom.: 0 AF XY: 0.0000295 AC XY: 4AN XY: 135786
GnomAD4 exome AF: 0.0000192 AC: 28AN: 1461858Hom.: 0 Cov.: 32 AF XY: 0.0000193 AC XY: 14AN XY: 727226
GnomAD4 genome ? AF: 0.00000658 AC: 1AN: 152036Hom.: 0 Cov.: 31 AF XY: 0.00 AC XY: 0AN XY: 74242
ClinVar
Submissions by phenotype
Aicardi-Goutieres syndrome 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Apr 11, 2023 | - - |
Inborn genetic diseases Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Jul 09, 2021 | The c.2548C>T (p.R850W) alteration is located in exon 8 (coding exon 8) of the ADAR gene. This alteration results from a C to T substitution at nucleotide position 2548, causing the arginine (R) at amino acid position 850 to be replaced by a tryptophan (W). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Symmetrical dyschromatosis of extremities;C3539013:Aicardi-Goutieres syndrome 6 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 27, 2023 | This sequence change replaces arginine, which is basic and polar, with tryptophan, which is neutral and slightly polar, at codon 850 of the ADAR protein (p.Arg850Trp). This variant is present in population databases (rs762568334, gnomAD 0.009%). This variant has not been reported in the literature in individuals affected with ADAR-related conditions. ClinVar contains an entry for this variant (Variation ID: 540262). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt ADAR protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at