GeneBe

rs10814952

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_203447.4(DOCK8):​c.5581-18G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
Exomes 𝑓: 0.0 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

DOCK8
NM_203447.4 intron

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -1.34

Publications

11 publications found
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 Gene-Disease associations (from GenCC):
  • combined immunodeficiency due to DOCK8 deficiency
    Inheritance: AR Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, ClinGen, Labcorp Genetics (formerly Invitae), G2P, Ambry Genetics, Genomics England PanelApp
  • autosomal dominant non-syndromic intellectual disability
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • complex neurodevelopmental disorder
    Inheritance: AD Classification: LIMITED Submitted by: Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.86).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_203447.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DOCK8
NM_203447.4
MANE Select
c.5581-18G>A
intron
N/ANP_982272.2
DOCK8
NM_001193536.2
c.5377-18G>A
intron
N/ANP_001180465.1
DOCK8
NM_001190458.2
c.5281-18G>A
intron
N/ANP_001177387.1

Ensembl Transcripts

Selected
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
DOCK8
ENST00000432829.7
TSL:1 MANE Select
c.5581-18G>A
intron
N/AENSP00000394888.3
DOCK8
ENST00000469391.5
TSL:1
c.5281-18G>A
intron
N/AENSP00000419438.1
DOCK8
ENST00000382329.2
TSL:1
c.5281-18G>A
intron
N/AENSP00000371766.2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
1454304
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
724126
African (AFR)
AF:
0.00
AC:
0
AN:
33296
American (AMR)
AF:
0.00
AC:
0
AN:
44704
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
26082
East Asian (EAS)
AF:
0.00
AC:
0
AN:
39676
South Asian (SAS)
AF:
0.00
AC:
0
AN:
86046
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
53400
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5766
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
1105228
Other (OTH)
AF:
0.00
AC:
0
AN:
60106
GnomAD4 genome
Cov.:
33
Alfa
AF:
0.00
Hom.:
3708

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.86
CADD
Benign
2.5
DANN
Benign
0.95
PhyloP100
-1.3

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

Other links and lift over

dbSNP: rs10814952; hg19: chr9-446352; API