rs369412510
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_203447.4(DOCK8):c.539G>A(p.Arg180His) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000644 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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. R180C) has been classified as Likely benign.
Frequency
Consequence
NM_203447.4 missense
Scores
Clinical Significance
Conservation
Genome browser will be placed here
ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK8 | NM_203447.4 | c.539G>A | p.Arg180His | missense_variant | 6/48 | ENST00000432829.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK8 | ENST00000432829.7 | c.539G>A | p.Arg180His | missense_variant | 6/48 | 1 | NM_203447.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000131 AC: 20AN: 152160Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000128 AC: 32AN: 249660Hom.: 0 AF XY: 0.000148 AC XY: 20AN XY: 135120
GnomAD4 exome AF: 0.0000575 AC: 84AN: 1461532Hom.: 0 Cov.: 31 AF XY: 0.0000701 AC XY: 51AN XY: 727050
GnomAD4 genome ? AF: 0.000131 AC: 20AN: 152278Hom.: 0 Cov.: 32 AF XY: 0.000161 AC XY: 12AN XY: 74464
ClinVar
Submissions by phenotype
Combined immunodeficiency due to DOCK8 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Sep 05, 2022 | This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 180 of the DOCK8 protein (p.Arg180His). This variant is present in population databases (rs369412510, gnomAD 0.07%). This variant has not been reported in the literature in individuals affected with DOCK8-related conditions. ClinVar contains an entry for this variant (Variation ID: 571149). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Tolerated"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The histidine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect 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