rs549052303

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The XM_047423927.1(DOCK8):​c.-152+3432C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000525 in 1,524,280 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 34)
Exomes 𝑓: 0.0000029 ( 0 hom. )

Consequence

DOCK8
XM_047423927.1 intron

Scores

1
15

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.147
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]
DOCK8-AS1 (HGNC:26436): (DOCK8 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.15941888).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
DOCK8NM_203447.4 linkc.-229C>A upstream_gene_variant ENST00000432829.7 NP_982272.2 Q8NF50-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
DOCK8ENST00000432829.7 linkc.-229C>A upstream_gene_variant 1 NM_203447.4 ENSP00000394888.3 Q8NF50-1

Frequencies

GnomAD3 genomes
AF:
0.0000197
AC:
3
AN:
152084
Hom.:
0
Cov.:
34
show subpopulations
Gnomad AFR
AF:
0.0000724
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
GnomAD4 exome
AF:
0.00000292
AC:
4
AN:
1372086
Hom.:
0
Cov.:
85
AF XY:
0.00
AC XY:
0
AN XY:
676804
show subpopulations
Gnomad4 AFR exome
AF:
0.0000353
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000187
Gnomad4 OTH exome
AF:
0.0000176
GnomAD4 genome
AF:
0.0000263
AC:
4
AN:
152194
Hom.:
0
Cov.:
34
AF XY:
0.0000269
AC XY:
2
AN XY:
74410
show subpopulations
Gnomad4 AFR
AF:
0.0000963
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
Alfa
AF:
0.0000348
Hom.:
0
Bravo
AF:
0.0000151
Asia WGS
AF:
0.000289
AC:
1
AN:
3470

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
-0.23
T
BayesDel_noAF
Benign
-0.57
CADD
Benign
13
DANN
Benign
0.89
DEOGEN2
Benign
0.062
T
Eigen
Benign
-0.30
Eigen_PC
Benign
-0.46
FATHMM_MKL
Benign
0.22
N
LIST_S2
Benign
0.35
T
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.16
T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
0.0
N
PROVEAN
Uncertain
-3.9
D
REVEL
Benign
0.056
Sift4G
Benign
0.083
T
Polyphen
1.0
D
Vest4
0.17
MutPred
0.25
Loss of relative solvent accessibility (P = 0.0186);
MVP
0.14
MPC
0.62
ClinPred
0.78
D
GERP RS
2.4
Varity_R
0.65
gMVP
0.015

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: rs549052303; hg19: chr9-214748; API