rs146250176
Variant summary
Our verdict is Benign. Variant got -7 ACMG points: 2P and 9B. PM2BP4_StrongBP6BS1
The NM_203447.4(DOCK8):c.1582C>A(p.Leu528Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000342 in 1,614,158 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).
Frequency
Consequence
NM_203447.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -7 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK8 | NM_203447.4 | c.1582C>A | p.Leu528Met | missense_variant | 14/48 | ENST00000432829.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK8 | ENST00000432829.7 | c.1582C>A | p.Leu528Met | missense_variant | 14/48 | 1 | NM_203447.4 |
Frequencies
GnomAD3 genomes ? AF: 0.00197 AC: 300AN: 152178Hom.: 1 Cov.: 32
GnomAD3 exomes AF: 0.000442 AC: 111AN: 251312Hom.: 1 AF XY: 0.000309 AC XY: 42AN XY: 135818
GnomAD4 exome AF: 0.000172 AC: 251AN: 1461862Hom.: 0 Cov.: 30 AF XY: 0.000142 AC XY: 103AN XY: 727242
GnomAD4 genome ? AF: 0.00198 AC: 301AN: 152296Hom.: 1 Cov.: 32 AF XY: 0.00180 AC XY: 134AN XY: 74462
ClinVar
Submissions by phenotype
Combined immunodeficiency due to DOCK8 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Baylor Genetics | Aug 08, 2018 | This variant was determined to be of uncertain significance according to ACMG Guidelines, 2015 [PMID:25741868]. - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Apr 02, 2021 | - - |
Autosomal recessive hyper-IgE syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 14, 2024 | - - |
not provided Benign:1
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 09, 2018 | - - |
DOCK8-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | May 27, 2022 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at