rs151094543
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_203447.4(DOCK8):āc.3058A>Gā(p.Ile1020Val) variant causes a missense change. The variant allele was found at a frequency of 0.00047 in 1,614,110 control chromosomes in the GnomAD database, including 6 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I1020M) has been classified as Uncertain significance.
Frequency
Consequence
NM_203447.4 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -13 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK8 | NM_203447.4 | c.3058A>G | p.Ile1020Val | missense_variant | 25/48 | ENST00000432829.7 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK8 | ENST00000432829.7 | c.3058A>G | p.Ile1020Val | missense_variant | 25/48 | 1 | NM_203447.4 |
Frequencies
GnomAD3 genomes AF: 0.000473 AC: 72AN: 152158Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.000481 AC: 121AN: 251428Hom.: 2 AF XY: 0.000552 AC XY: 75AN XY: 135904
GnomAD4 exome AF: 0.000469 AC: 686AN: 1461834Hom.: 6 Cov.: 32 AF XY: 0.000495 AC XY: 360AN XY: 727214
GnomAD4 genome AF: 0.000473 AC: 72AN: 152276Hom.: 0 Cov.: 32 AF XY: 0.000510 AC XY: 38AN XY: 74464
ClinVar
Submissions by phenotype
not provided Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jul 20, 2018 | This variant is associated with the following publications: (PMID: 32108967) - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2023 | DOCK8: BP4 - |
Combined immunodeficiency due to DOCK8 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score, this variant could not be ruled out of causing disease and therefore its association with disease required further investigation. A literature search was performed for the gene, cDNA change, and amino acid change (if applicable). No publications were found based on this search. This variant was therefore classified as a variant of unknown significance for this disease. - |
DOCK8-related disorder Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Nov 21, 2022 | The DOCK8 c.3058A>G variant is predicted to result in the amino acid substitution p.Ile1020Val. This variant was reported in the homozygous state in two individuals with DOCK8 deficiency (reported as rs151094543 in Table 1, Haskologlu et al 2020. PubMed ID: 32108967). This variant in interpreted as benign/likely benign/uncertain in ClinVar (https://preview.ncbi.nlm.nih.gov/clinvar/variation/218873/). This variant is reported in 0.091% of alleles in individuals of South Asian descent, including two homozygotes, in gnomAD (http://gnomad.broadinstitute.org/variant/9-396872-A-G). At this time, the clinical significance of this variant is uncertain due to the absence of conclusive functional and genetic evidence. - |
Autosomal recessive hyper-IgE syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genomic Diagnostic Laboratory, Division of Genomic Diagnostics, Children's Hospital of Philadelphia | Jul 24, 2015 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at