10-127024763-C-T
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001290223.2(DOCK1):c.1531C>T(p.Arg511Cys) variant causes a missense change. The variant allele was found at a frequency of 0.0000782 in 1,610,678 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000086 ( 0 hom. )
Consequence
DOCK1
NM_001290223.2 missense
NM_001290223.2 missense
Scores
2
9
8
Clinical Significance
Conservation
PhyloP100: 4.93
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 3 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, DOCK1
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK1 | NM_001290223.2 | c.1531C>T | p.Arg511Cys | missense_variant | 15/52 | ENST00000623213.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK1 | ENST00000623213.2 | c.1531C>T | p.Arg511Cys | missense_variant | 15/52 | 1 | NM_001290223.2 | ||
ENST00000420941.2 | n.204+1509G>A | intron_variant, non_coding_transcript_variant | 3 | ||||||
ENST00000601242.5 | n.151+1509G>A | intron_variant, non_coding_transcript_variant | 5 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152142Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.0000245 AC: 6AN: 244434Hom.: 0 AF XY: 0.0000302 AC XY: 4AN XY: 132322
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GnomAD4 exome AF: 0.0000857 AC: 125AN: 1458536Hom.: 0 Cov.: 30 AF XY: 0.0000883 AC XY: 64AN XY: 725044
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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 | Jan 23, 2023 | The c.1468C>T (p.R490C) alteration is located in exon 15 (coding exon 15) of the DOCK1 gene. This alteration results from a C to T substitution at nucleotide position 1468, causing the arginine (R) at amino acid position 490 to be replaced by a cysteine (C). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Uncertain
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Uncertain
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Benign
T;T
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D
M_CAP
Benign
T
MetaRNN
Uncertain
T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.
MutationTaster
Benign
D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
N;.
REVEL
Benign
Sift
Benign
T;.
Sift4G
Benign
T;T
Polyphen
P;.
Vest4
MutPred
Gain of catalytic residue at W491 (P = 0.0013);.;
MVP
MPC
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
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