rs199803893
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP2
The NM_001367561.1(DOCK7):āc.760C>Gā(p.Pro254Ala) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0000617 in 1,458,186 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: not found (cov: 32)
Exomes š: 0.000062 ( 0 hom. )
Consequence
DOCK7
NM_001367561.1 missense
NM_001367561.1 missense
Scores
2
6
10
Clinical Significance
Conservation
PhyloP100: 9.75
Genes affected
DOCK7 (HGNC:19190): (dedicator of cytokinesis 7) The protein encoded by this gene is a guanine nucleotide exchange factor (GEF) that plays a role in axon formation and neuronal polarization. The encoded protein displays GEF activity toward RAC1 and RAC3 Rho small GTPases but not toward CDC42. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Dec 2012]
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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, DOCK7
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK7 | NM_001367561.1 | c.760C>G | p.Pro254Ala | missense_variant | 7/50 | ENST00000635253.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK7 | ENST00000635253.2 | c.760C>G | p.Pro254Ala | missense_variant | 7/50 | 5 | NM_001367561.1 |
Frequencies
GnomAD3 genomes ? Cov.: 32
GnomAD3 genomes
?
Cov.:
32
GnomAD3 exomes AF: 0.0000161 AC: 4AN: 248104Hom.: 0 AF XY: 0.0000224 AC XY: 3AN XY: 134120
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GnomAD4 exome AF: 0.0000617 AC: 90AN: 1458186Hom.: 0 Cov.: 29 AF XY: 0.0000634 AC XY: 46AN XY: 725302
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725302
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GnomAD4 genome ? Cov.: 32
GnomAD4 genome
?
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32
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3
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 23 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | Apr 12, 2022 | This sequence change replaces proline, which is neutral and non-polar, with alanine, which is neutral and non-polar, at codon 254 of the DOCK7 protein (p.Pro254Ala). This variant is present in population databases (rs199803893, gnomAD 0.004%). This variant has not been reported in the literature in individuals affected with DOCK7-related conditions. ClinVar contains an entry for this variant (Variation ID: 475170). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated. 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:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Pathogenic
DANN
Benign
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Uncertain
D;D;D;D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
L;L;L;L;L;L;L
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Pathogenic
D;.;D;.;.;.;D
REVEL
Uncertain
Sift
Benign
T;.;T;.;.;.;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
0.47, 0.088, 0.83, 0.94
.;P;B;P;P;.;.
Vest4
MutPred
Loss of ubiquitination at K258 (P = 0.0439);Loss of ubiquitination at K258 (P = 0.0439);Loss of ubiquitination at K258 (P = 0.0439);Loss of ubiquitination at K258 (P = 0.0439);Loss of ubiquitination at K258 (P = 0.0439);Loss of ubiquitination at K258 (P = 0.0439);Loss of ubiquitination at K258 (P = 0.0439);
MVP
MPC
0.58
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at