9-434894-G-C
Variant summary
Our verdict is Benign. Variant got -11 ACMG points: 2P and 13B. PM2BP4_StrongBP6_Very_StrongBP7
The NM_203447.4(DOCK8):c.4998G>C(p.Val1666=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000156 in 1,613,810 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00011 ( 0 hom., cov: 33)
Exomes 𝑓: 0.00016 ( 0 hom. )
Consequence
DOCK8
NM_203447.4 synonymous
NM_203447.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.00600
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 -11 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.53).
BP6
?
Variant 9-434894-G-C is Benign according to our data. Variant chr9-434894-G-C is described in ClinVar as [Likely_benign]. Clinvar id is 504725.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-434894-G-C is described in Lovd as [Likely_benign].
BP7
?
Synonymous conserved (PhyloP=0.006 with no splicing effect.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK8 | NM_203447.4 | c.4998G>C | p.Val1666= | synonymous_variant | 39/48 | ENST00000432829.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK8 | ENST00000432829.7 | c.4998G>C | p.Val1666= | synonymous_variant | 39/48 | 1 | NM_203447.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000112 AC: 17AN: 152202Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.0000956 AC: 24AN: 251128Hom.: 0 AF XY: 0.0000958 AC XY: 13AN XY: 135722
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GnomAD4 exome AF: 0.000160 AC: 234AN: 1461608Hom.: 0 Cov.: 32 AF XY: 0.000164 AC XY: 119AN XY: 727100
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ClinVar
Significance: Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Likely benign, criteria provided, single submitter | clinical testing | Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine | Jul 28, 2016 | p.Val1666Val in exon 39 of DOCK8: This variant is not expected to have clinical significance because it does not alter an amino acid residue and is not located within the splice consensus sequence. It has been identified in 11/66580 Europea n chromosomes by the Exome Aggregation Consortium (ExAC, http://exac.broadinsti tute.org; dbSNP rs370901183). - |
Likely benign, no assertion criteria provided | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 13, 2022 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2024 | DOCK8: BP4, BP7 - |
Autosomal recessive hyper-IgE syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Jan 29, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
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