rs199940668
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong
The NM_203447.4(DOCK8):c.1286-5T>A 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 0.0000353 in 1,614,060 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Consequence
NM_203447.4 splice_region, splice_polypyrimidine_tract, intron
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK8 | NM_203447.4 | c.1286-5T>A | 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.1286-5T>A | splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_203447.4 |
Frequencies
GnomAD3 genomes ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.00000796 AC: 2AN: 251372Hom.: 0 AF XY: 0.0000147 AC XY: 2AN XY: 135852
GnomAD4 exome AF: 0.0000376 AC: 55AN: 1461850Hom.: 0 Cov.: 32 AF XY: 0.0000413 AC XY: 30AN XY: 727230
GnomAD4 genome ? AF: 0.0000131 AC: 2AN: 152210Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0AN XY: 74358
ClinVar
Submissions by phenotype
Combined immunodeficiency due to DOCK8 deficiency Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Aug 23, 2022 | This sequence change falls in intron 11 of the DOCK8 gene. It does not directly change the encoded amino acid sequence of the DOCK8 protein. This variant is present in population databases (rs199940668, gnomAD 0.002%). This variant has not been reported in the literature in individuals affected with DOCK8-related conditions. ClinVar contains an entry for this variant (Variation ID: 536599). Algorithms developed to predict the effect of sequence changes on RNA splicing suggest that this variant may disrupt the consensus splice site. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at