rs767858333
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Variant summary
Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_001290223.2(DOCK1):c.2053dup(p.Glu685GlyfsTer6) variant causes a frameshift change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000616 in 1,461,862 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Likely pathogenic (★). Variant results in nonsense mediated mRNA decay.
Frequency
Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000062 ( 0 hom. )
Consequence
DOCK1
NM_001290223.2 frameshift
NM_001290223.2 frameshift
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 9.90
Genes affected
DOCK1 (HGNC:2987): (dedicator of cytokinesis 1) This gene encodes a member of the dedicator of cytokinesis protein family. Dedicator of cytokinesis proteins act as guanine nucleotide exchange factors for small Rho family G proteins. The encoded protein regulates the small GTPase Rac, thereby influencing several biological processes, including phagocytosis and cell migration. Overexpression of this gene has also been associated with certain cancers. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Mar 2014]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 4 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP5
?
Variant 10-127042665-T-TG is Pathogenic according to our data. Variant chr10-127042665-T-TG is described in ClinVar as [Likely_pathogenic]. Clinvar id is 521686.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK1 | NM_001290223.2 | c.2053dup | p.Glu685GlyfsTer6 | frameshift_variant | 20/52 | ENST00000623213.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK1 | ENST00000623213.2 | c.2053dup | p.Glu685GlyfsTer6 | frameshift_variant | 20/52 | 1 | NM_001290223.2 | ||
DOCK1 | ENST00000280333.9 | c.1990dup | p.Glu664GlyfsTer6 | frameshift_variant | 20/52 | 1 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.0000160 AC: 4AN: 249564Hom.: 0 AF XY: 0.0000148 AC XY: 2AN XY: 135392
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727238
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GnomAD4 genome ? Cov.: 33
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ClinVar
Significance: Likely pathogenic
Submissions summary: Pathogenic:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Inborn genetic diseases Pathogenic:1
Likely pathogenic, criteria provided, single submitter | clinical testing | Ambry Genetics | May 17, 2017 | Lines of evidence used in support of classification: SUSPECTED CANDIDATE: Alteration(s) of Potential Clinical Relevance Detected - |
Computational scores
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SpliceAI score (max)
Details are displayed if max score is > 0.2
DS_AL_spliceai
Position offset: -40
Find out detailed SpliceAI scores and Pangolin per-transcript scores at