rs141501849
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 3P and 16B. PM2PP2BP4_StrongBP6_Very_StrongBS1
The NM_004946.3(DOCK2):āc.2587A>Gā(p.Lys863Glu) variant causes a missense change. The variant allele was found at a frequency of 0.000231 in 1,614,192 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.00095 ( 0 hom., cov: 32)
Exomes š: 0.00016 ( 0 hom. )
Consequence
DOCK2
NM_004946.3 missense
NM_004946.3 missense
Scores
4
14
Clinical Significance
Conservation
PhyloP100: 6.31
Genes affected
DOCK2 (HGNC:2988): (dedicator of cytokinesis 2) The protein encoded by this gene belongs to the CDM protein family. It is specifically expressed in hematopoietic cells and is predominantly expressed in peripheral blood leukocytes. The protein is involved in remodeling of the actin cytoskeleton required for lymphocyte migration in response to chemokine signaling. It activates members of the Rho family of GTPases, for example RAC1 and RAC2, by acting as a guanine nucleotide exchange factor (GEF) to exchange bound GDP for free GTP. Mutations in this gene result in immunodeficiency 40 (IMD40), a combined form of immunodeficiency that affects T cell number and function, also with variable defects in B cell and NK cell function. [provided by RefSeq, May 2018]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, DOCK2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.015455216).
BP6
?
Variant 5-169803090-A-G is Benign according to our data. Variant chr5-169803090-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 542631.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000945 (144/152328) while in subpopulation AFR AF= 0.00303 (126/41572). AF 95% confidence interval is 0.0026. There are 0 homozygotes in gnomad4. There are 71 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK2 | NM_004946.3 | c.2587A>G | p.Lys863Glu | missense_variant | 26/52 | ENST00000520908.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK2 | ENST00000520908.7 | c.2587A>G | p.Lys863Glu | missense_variant | 26/52 | 2 | NM_004946.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000939 AC: 143AN: 152210Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000235 AC: 59AN: 251164Hom.: 0 AF XY: 0.000228 AC XY: 31AN XY: 135730
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GnomAD4 exome AF: 0.000157 AC: 229AN: 1461864Hom.: 0 Cov.: 31 AF XY: 0.000157 AC XY: 114AN XY: 727234
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GnomAD4 genome ? AF: 0.000945 AC: 144AN: 152328Hom.: 0 Cov.: 32 AF XY: 0.000953 AC XY: 71AN XY: 74494
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
DOCK2 deficiency Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 05, 2024 | - - |
DOCK2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Feb 24, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;.;T
Eigen
Benign
Eigen_PC
Uncertain
FATHMM_MKL
Uncertain
D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;.;N
REVEL
Benign
Sift
Benign
T;.;.;T
Sift4G
Benign
T;.;T;T
Polyphen
B;B;.;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at