chr10-127042665-T-TG
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2PP5_Moderate
The NM_001290223.2(DOCK1):c.2053dupG(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
Publications
0 publications found
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 was made for transcript
Our verdict: Uncertain_significance. The variant received 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 VariationId is 521686.Status of the report is criteria_provided_single_submitter, 1 stars.
Variant Effect in Transcripts
ACMG analysis was done for transcript: NM_001290223.2. You can select a different transcript below to see updated ACMG assignments.
RefSeq Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DOCK1 | NM_001290223.2 | MANE Select | c.2053dupG | p.Glu685GlyfsTer6 | frameshift | Exon 20 of 52 | NP_001277152.2 | ||
| DOCK1 | NM_001377543.1 | c.1990dupG | p.Glu664GlyfsTer6 | frameshift | Exon 20 of 53 | NP_001364472.1 | |||
| DOCK1 | NM_001377544.1 | c.2026dupG | p.Glu676GlyfsTer6 | frameshift | Exon 21 of 53 | NP_001364473.1 |
Ensembl Transcripts
| Selected | Gene | Transcript | Tags | HGVSc | HGVSp | Effect | Exon Rank | Protein | UniProt |
|---|---|---|---|---|---|---|---|---|---|
| DOCK1 | ENST00000623213.2 | TSL:1 MANE Select | c.2053dupG | p.Glu685GlyfsTer6 | frameshift | Exon 20 of 52 | ENSP00000485033.1 | ||
| DOCK1 | ENST00000280333.9 | TSL:1 | c.1990dupG | p.Glu664GlyfsTer6 | frameshift | Exon 20 of 52 | ENSP00000280333.6 |
Frequencies
GnomAD3 genomes
GnomAD3 genomes
Cov.:
33
GnomAD2 exomes AF: 0.0000160 AC: 4AN: 249564 AF XY: 0.0000148 show subpopulations
GnomAD2 exomes
AF:
AC:
4
AN:
249564
AF XY:
Gnomad AFR exome
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Gnomad ASJ exome
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Gnomad EAS exome
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Gnomad FIN exome
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Gnomad NFE exome
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Gnomad OTH exome
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GnomAD4 exome AF: 0.00000616 AC: 9AN: 1461862Hom.: 0 Cov.: 32 AF XY: 0.00000963 AC XY: 7AN XY: 727238 show subpopulations
GnomAD4 exome
AF:
AC:
9
AN:
1461862
Hom.:
Cov.:
32
AF XY:
AC XY:
7
AN XY:
727238
show subpopulations
African (AFR)
AF:
AC:
1
AN:
33480
American (AMR)
AF:
AC:
2
AN:
44724
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26136
East Asian (EAS)
AF:
AC:
0
AN:
39700
South Asian (SAS)
AF:
AC:
0
AN:
86258
European-Finnish (FIN)
AF:
AC:
0
AN:
53420
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
6
AN:
1111980
Other (OTH)
AF:
AC:
0
AN:
60396
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.464
Heterozygous variant carriers
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Allele balance
Age Distribution
Exome Het
Variant carriers
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GnomAD4 genome
GnomAD4 genome
Cov.:
33
Alfa
AF:
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Bravo
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ClinVar
ClinVar submissions as Germline
Significance:Likely pathogenic
Revision:criteria provided, single submitter
Pathogenic
VUS
Benign
Condition
1
-
-
Inborn genetic diseases (1)
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
PhyloP100
Splicing
Name
Calibrated prediction
Score
Prediction
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
Publications
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