rs767478064
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Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM2BP6_Very_StrongBS1
The NM_203447.4(DOCK8):c.5962-16_5962-8del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000325 in 578,636 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.00073 ( 0 hom., cov: 21)
Exomes 𝑓: 0.00025 ( 0 hom. )
Consequence
DOCK8
NM_203447.4 splice_region, splice_polypyrimidine_tract, intron
NM_203447.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.64
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 -10 ACMG points.
PM2
Very rare variant in population databases, with high coverage;
BP6
Variant 9-451994-TTTTTTTTTC-T is Benign according to our data. Variant chr9-451994-TTTTTTTTTC-T is described in ClinVar as [Likely_benign]. Clinvar id is 536611.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr9-451994-TTTTTTTTTC-T is described in Lovd as [Likely_benign].
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000733 (69/94188) while in subpopulation NFE AF= 0.00139 (56/40318). AF 95% confidence interval is 0.0011. There are 0 homozygotes in gnomad4. There are 26 alleles in male gnomad4 subpopulation. Median coverage is 21. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK8 | NM_203447.4 | c.5962-16_5962-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | ENST00000432829.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK8 | ENST00000432829.7 | c.5962-16_5962-8del | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_203447.4 |
Frequencies
GnomAD3 genomes AF: 0.000733 AC: 69AN: 94158Hom.: 0 Cov.: 21
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GnomAD4 exome AF: 0.000246 AC: 119AN: 484448Hom.: 0 AF XY: 0.000270 AC XY: 70AN XY: 258796
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GnomAD4 genome AF: 0.000733 AC: 69AN: 94188Hom.: 0 Cov.: 21 AF XY: 0.000582 AC XY: 26AN XY: 44658
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ClinVar
Significance: Likely benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Autosomal recessive hyper-IgE syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Sep 04, 2023 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Apr 01, 2023 | DOCK8: BP4 - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at