rs145968092
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Variant summary
Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_StrongBP6_ModerateBP7BS1BS2
The NM_203447.4(DOCK8):āc.1371T>Cā(p.Val457=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000125 in 1,614,160 control chromosomes in the GnomAD database, including 3 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ).
Frequency
Genomes: š 0.00053 ( 1 hom., cov: 32)
Exomes š: 0.000082 ( 2 hom. )
Consequence
DOCK8
NM_203447.4 synonymous
NM_203447.4 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.545
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.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
?
Variant 9-336667-T-C is Benign according to our data. Variant chr9-336667-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 468734.Status of the report is criteria_provided_single_submitter, 1 stars.
BP7
?
Synonymous conserved (PhyloP=-0.545 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.000532 (81/152300) while in subpopulation AFR AF= 0.00183 (76/41564). AF 95% confidence interval is 0.0015. There are 1 homozygotes in gnomad4. There are 38 alleles in male gnomad4 subpopulation. Median coverage is 32. This position pass quality control queck.
BS2
?
High Homozygotes in GnomAdExome4 at 2 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK8 | NM_203447.4 | c.1371T>C | p.Val457= | synonymous_variant | 12/48 | ENST00000432829.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK8 | ENST00000432829.7 | c.1371T>C | p.Val457= | synonymous_variant | 12/48 | 1 | NM_203447.4 |
Frequencies
GnomAD3 genomes ? AF: 0.000532 AC: 81AN: 152182Hom.: 1 Cov.: 32
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GnomAD3 exomes AF: 0.000151 AC: 38AN: 251394Hom.: 0 AF XY: 0.000118 AC XY: 16AN XY: 135864
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GnomAD4 exome AF: 0.0000821 AC: 120AN: 1461860Hom.: 2 Cov.: 32 AF XY: 0.0000646 AC XY: 47AN XY: 727234
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GnomAD4 genome ? AF: 0.000532 AC: 81AN: 152300Hom.: 1 Cov.: 32 AF XY: 0.000510 AC XY: 38AN XY: 74476
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Autosomal recessive hyper-IgE syndrome Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Invitae | Nov 24, 2023 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
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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