rs142208336
Positions:
Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 2P and 17B. PM2BP4_StrongBP6_Very_StrongBP7BS1
The NM_203447.4(DOCK8):c.5010G>A(p.Ala1670=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000304 in 1,613,840 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.0012 ( 1 hom., cov: 33)
Exomes 𝑓: 0.00021 ( 0 hom. )
Consequence
DOCK8
NM_203447.4 synonymous
NM_203447.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.509
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -15 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.65).
BP6
?
Variant 9-434906-G-A is Benign according to our data. Variant chr9-434906-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 536614.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=-0.509 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00116 (177/152296) while in subpopulation AFR AF= 0.00416 (173/41568). AF 95% confidence interval is 0.00366. There are 1 homozygotes in gnomad4. There are 89 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK8 | NM_203447.4 | c.5010G>A | p.Ala1670= | synonymous_variant | 39/48 | ENST00000432829.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK8 | ENST00000432829.7 | c.5010G>A | p.Ala1670= | synonymous_variant | 39/48 | 1 | NM_203447.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00114 AC: 173AN: 152178Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.000378 AC: 95AN: 251034Hom.: 0 AF XY: 0.000258 AC XY: 35AN XY: 135652
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GnomAD4 exome AF: 0.000215 AC: 314AN: 1461544Hom.: 0 Cov.: 32 AF XY: 0.000171 AC XY: 124AN XY: 727080
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GnomAD4 genome ? AF: 0.00116 AC: 177AN: 152296Hom.: 1 Cov.: 33 AF XY: 0.00120 AC XY: 89AN XY: 74464
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive hyper-IgE syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 19, 2021 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Oct 01, 2023 | DOCK8: BP4, BP7 - |
Computational scores
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
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