chr10-126981957-A-G
Variant summary
Our verdict is Likely benign. Variant got -1 ACMG points: 3P and 4B. PM2PP2BP4_Strong
The NM_001290223.2(DOCK1):c.211A>G(p.Ile71Val) variant causes a missense change. The variant allele was found at a frequency of 0.000778 in 1,613,442 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.00049 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00081 ( 0 hom. )
Consequence
DOCK1
NM_001290223.2 missense
NM_001290223.2 missense
Scores
1
18
Clinical Significance
Conservation
PhyloP100: 5.49
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 Likely_benign. Variant got -1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, DOCK1
BP4
?
Computational evidence support a benign effect (MetaRNN=0.028178483).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK1 | NM_001290223.2 | c.211A>G | p.Ile71Val | missense_variant | 4/52 | ENST00000623213.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK1 | ENST00000623213.2 | c.211A>G | p.Ile71Val | missense_variant | 4/52 | 1 | NM_001290223.2 | ||
DOCK1 | ENST00000280333.9 | c.211A>G | p.Ile71Val | missense_variant | 4/52 | 1 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000487 AC: 74AN: 151970Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000486 AC: 121AN: 248910Hom.: 0 AF XY: 0.000533 AC XY: 72AN XY: 135056
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GnomAD4 exome AF: 0.000809 AC: 1182AN: 1461472Hom.: 0 Cov.: 31 AF XY: 0.000838 AC XY: 609AN XY: 727002
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GnomAD4 genome ? AF: 0.000487 AC: 74AN: 151970Hom.: 0 Cov.: 32 AF XY: 0.000350 AC XY: 26AN XY: 74236
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Feb 03, 2023 | The c.211A>G (p.I71V) alteration is located in exon 4 (coding exon 4) of the DOCK1 gene. This alteration results from a A to G substitution at nucleotide position 211, causing the isoleucine (I) at amino acid position 71 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Benign
DEOGEN2
Benign
T;T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.
MutationTaster
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
B;.
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at