9-312124-T-G

Position:

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_203447.4(DOCK8):ā€‹c.699T>Gā€‹(p.Asn233Lys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,986 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. N233N) has been classified as Benign.

Frequency

Genomes: š‘“ 0.000013 ( 0 hom., cov: 33)
Exomes š‘“: 0.0000034 ( 0 hom. )

Consequence

DOCK8
NM_203447.4 missense

Scores

1
6
12

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.300
Variant links:
Genes affected
DOCK8 (HGNC:19191): (dedicator of cytokinesis 8) This gene encodes a member of the DOCK180 family of guanine nucleotide exchange factors. Guanine nucleotide exchange factors interact with Rho GTPases and are components of intracellular signaling networks. Mutations in this gene result in the autosomal recessive form of the hyper-IgE syndrome. Alternatively spliced transcript variants encoding different isoforms have been described.[provided by RefSeq, Jun 2010]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
DOCK8NM_203447.4 linkc.699T>G p.Asn233Lys missense_variant 6/48 ENST00000432829.7 NP_982272.2 Q8NF50-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
DOCK8ENST00000432829.7 linkc.699T>G p.Asn233Lys missense_variant 6/481 NM_203447.4 ENSP00000394888.3 Q8NF50-1

Frequencies

GnomAD3 genomes
AF:
0.0000131
AC:
2
AN:
152106
Hom.:
0
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0000483
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251196
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135792
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.0000327
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000342
AC:
5
AN:
1461880
Hom.:
0
Cov.:
33
AF XY:
0.00000688
AC XY:
5
AN XY:
727238
show subpopulations
Gnomad4 AFR exome
AF:
0.0000299
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.0000348
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000131
AC:
2
AN:
152106
Hom.:
0
Cov.:
33
AF XY:
0.0000135
AC XY:
1
AN XY:
74290
show subpopulations
Gnomad4 AFR
AF:
0.0000483
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.24
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.48
CADD
Benign
14
DANN
Uncertain
1.0
DEOGEN2
Benign
0.32
T;.;.
Eigen
Benign
-0.33
Eigen_PC
Benign
-0.40
FATHMM_MKL
Benign
0.66
D
LIST_S2
Benign
0.85
D;T;T
M_CAP
Benign
0.013
T
MetaRNN
Uncertain
0.45
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Pathogenic
2.9
M;.;.
PrimateAI
Uncertain
0.58
T
PROVEAN
Uncertain
-2.8
.;.;D
REVEL
Benign
0.18
Sift
Uncertain
0.017
.;.;D
Sift4G
Uncertain
0.059
T;T;T
Polyphen
0.40
B;.;.
Vest4
0.60
MutPred
0.41
Gain of ubiquitination at N233 (P = 0.0104);.;.;
MVP
0.28
MPC
0.057
ClinPred
0.88
D
GERP RS
-2.5
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.49
gMVP
0.54

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs2039045; hg19: chr9-312124; API