rs201626676
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 1P and 14B. PP2BP4_StrongBP6_ModerateBS1BS2
The NM_004946.3(DOCK2):āc.1417A>Gā(p.Met473Val) variant causes a missense change. The variant allele was found at a frequency of 0.00209 in 1,614,058 control chromosomes in the GnomAD database, including 91 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (ā ).
Frequency
Genomes: š 0.0012 ( 6 hom., cov: 33)
Exomes š: 0.0022 ( 85 hom. )
Consequence
DOCK2
NM_004946.3 missense
NM_004946.3 missense
Scores
17
Clinical Significance
Conservation
PhyloP100: 6.44
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -13 ACMG points.
PP2
?
Missense variant where missense usually causes diseases, DOCK2
BP4
?
Computational evidence support a benign effect (MetaRNN=0.003529787).
BP6
?
Variant 5-169708202-A-G is Benign according to our data. Variant chr5-169708202-A-G is described in ClinVar as [Benign]. Clinvar id is 476000.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr5-169708202-A-G is described in Lovd as [Benign].
BS1
?
Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00122 (186/152382) while in subpopulation SAS AF= 0.037 (179/4834). AF 95% confidence interval is 0.0326. There are 6 homozygotes in gnomad4. There are 133 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAd4 at 6 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK2 | NM_004946.3 | c.1417A>G | p.Met473Val | missense_variant | 15/52 | ENST00000520908.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK2 | ENST00000520908.7 | c.1417A>G | p.Met473Val | missense_variant | 15/52 | 2 | NM_004946.3 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00123 AC: 188AN: 152264Hom.: 6 Cov.: 33
GnomAD3 genomes
?
AF:
AC:
188
AN:
152264
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00432 AC: 1083AN: 250656Hom.: 24 AF XY: 0.00594 AC XY: 805AN XY: 135438
GnomAD3 exomes
AF:
AC:
1083
AN:
250656
Hom.:
AF XY:
AC XY:
805
AN XY:
135438
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.00218 AC: 3192AN: 1461676Hom.: 85 Cov.: 31 AF XY: 0.00327 AC XY: 2375AN XY: 727124
GnomAD4 exome
AF:
AC:
3192
AN:
1461676
Hom.:
Cov.:
31
AF XY:
AC XY:
2375
AN XY:
727124
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.00122 AC: 186AN: 152382Hom.: 6 Cov.: 33 AF XY: 0.00178 AC XY: 133AN XY: 74522
GnomAD4 genome
?
AF:
AC:
186
AN:
152382
Hom.:
Cov.:
33
AF XY:
AC XY:
133
AN XY:
74522
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
TwinsUK
AF:
AC:
0
ALSPAC
AF:
AC:
1
ExAC
?
AF:
AC:
573
Asia WGS
AF:
AC:
61
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
DOCK2 deficiency Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 28, 2024 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;.
Polyphen
B;B
Vest4
MVP
MPC
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at