rs200973349
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 3P and 5B. PM2PP2BP4_StrongBS1_Supporting
The NM_004946.3(DOCK2):c.3366T>A(p.Ser1122Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000378 in 1,613,938 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 nucleotide change resulting in same amino acid change has been previously reported as Uncertain significancein ClinVar.
Frequency
Consequence
NM_004946.3 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK2 | NM_004946.3 | c.3366T>A | p.Ser1122Arg | missense_variant | 33/52 | ENST00000520908.7 | |
DOCK2 | NR_156756.1 | n.3469T>A | non_coding_transcript_exon_variant | 34/53 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK2 | ENST00000520908.7 | c.3366T>A | p.Ser1122Arg | missense_variant | 33/52 | 2 | NM_004946.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000243 AC: 37AN: 152064Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000757 AC: 19AN: 251064Hom.: 0 AF XY: 0.0000663 AC XY: 9AN XY: 135690
GnomAD4 exome AF: 0.0000171 AC: 25AN: 1461756Hom.: 0 Cov.: 30 AF XY: 0.0000151 AC XY: 11AN XY: 727174
GnomAD4 genome ? AF: 0.000237 AC: 36AN: 152182Hom.: 0 Cov.: 32 AF XY: 0.000175 AC XY: 13AN XY: 74424
ClinVar
Submissions by phenotype
DOCK2 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Jul 19, 2022 | This sequence change replaces serine, which is neutral and polar, with arginine, which is basic and polar, at codon 1122 of the DOCK2 protein (p.Ser1122Arg). This variant is present in population databases (rs200973349, gnomAD 0.09%). This variant has not been reported in the literature in individuals affected with DOCK2-related conditions. ClinVar contains an entry for this variant (Variation ID: 542606). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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