rs894086772
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 1 ACMG points: 3P and 2B. PM2PP2BP4_Moderate
The NM_001367561.1(DOCK7):āc.721T>Cā(p.Ser241Pro) variant causes a missense change. The variant allele was found at a frequency of 0.00000434 in 1,612,896 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ā ).
Frequency
Genomes: š 0.0000066 ( 0 hom., cov: 32)
Exomes š: 0.0000041 ( 0 hom. )
Consequence
DOCK7
NM_001367561.1 missense
NM_001367561.1 missense
Scores
2
16
Clinical Significance
Conservation
PhyloP100: 4.54
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 1 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
PP2
?
Missense variant where missense usually causes diseases, DOCK7
BP4
?
Computational evidence support a benign effect (MetaRNN=0.12212995).
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DOCK7 | NM_001367561.1 | c.721T>C | p.Ser241Pro | missense_variant | 6/50 | ENST00000635253.2 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DOCK7 | ENST00000635253.2 | c.721T>C | p.Ser241Pro | missense_variant | 6/50 | 5 | NM_001367561.1 |
Frequencies
GnomAD3 genomes ? AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32
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GnomAD4 exome AF: 0.00000411 AC: 6AN: 1460798Hom.: 0 Cov.: 31 AF XY: 0.00000688 AC XY: 5AN XY: 726732
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GnomAD4 genome ? AF: 0.00000657 AC: 1AN: 152098Hom.: 0 Cov.: 32 AF XY: 0.0000135 AC XY: 1AN XY: 74272
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Developmental and epileptic encephalopathy, 23 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Invitae | May 25, 2022 | This sequence change replaces serine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 241 of the DOCK7 protein (p.Ser241Pro). This variant is present in population databases (no rsID available, gnomAD 0.007%). 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: 475169). 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. - |
Seizure Uncertain:1
Uncertain significance, no assertion criteria provided | clinical testing | New York Genome Center | Jan 23, 2020 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
D;D;D;D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;N;N;N;N;N;N
MutationTaster
Benign
D;D;D
PrimateAI
Benign
T
PROVEAN
Benign
N;.;N;.;.;.;N
REVEL
Benign
Sift
Benign
T;.;T;.;.;.;T
Sift4G
Benign
T;T;T;T;T;T;T
Polyphen
0.0
.;B;B;B;B;.;.
Vest4
MutPred
Loss of phosphorylation at S241 (P = 0.0091);Loss of phosphorylation at S241 (P = 0.0091);Loss of phosphorylation at S241 (P = 0.0091);Loss of phosphorylation at S241 (P = 0.0091);Loss of phosphorylation at S241 (P = 0.0091);Loss of phosphorylation at S241 (P = 0.0091);Loss of phosphorylation at S241 (P = 0.0091);
MVP
MPC
0.49
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