rs587777034
Variant summary
Our verdict is Likely pathogenic. Variant got 8 ACMG points: 8P and 0B. PM1PM2PP3_ModeratePP5_Moderate
The NM_001098511.3(KIF2A):c.950G>A(p.Ser317Asn) variant causes a missense change involving the alteration of a conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Pathogenic (★).
Frequency
Genomes: not found (cov: 33)
Consequence
KIF2A
NM_001098511.3 missense
NM_001098511.3 missense
Scores
10
7
2
Clinical Significance
Conservation
PhyloP100: 10.0
Genes affected
KIF2A (HGNC:6318): (kinesin family member 2A) The protein encoded by this gene is a plus end-directed motor required for normal mitotic progression. The encoded protein is required for normal spindle activity during mitosis and is necessary for normal brain development. Several transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2011]
DIMT1 (HGNC:30217): (DIM1 rRNA methyltransferase and ribosome maturation factor) The protein encoded by this gene is a methyltransferase that is responsible for dimethylation of adjacent adenosines near the 18S rRNA decoding site. The encoded protein is essential for ribosome biogenesis, although its catalytic activity is not involved in the process. The yeast ortholog of this protein functions in the cytoplasm while this protein functions in the nucleus. [provided by RefSeq, Jan 2017]
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ACMG classification
Classification made for transcript
Verdict is Likely_pathogenic. Variant got 8 ACMG points.
PM1
?
In a binding_site (size 7) in uniprot entity KIF2A_HUMAN there are 5 pathogenic changes around while only 0 benign (100%) in NM_001098511.3
PM2
?
Very rare variant in population databases, with high coverage;
PP3
?
MetaRNN computational evidence supports a deleterious effect, 0.865
PP5
?
Variant 5-62361319-G-A is Pathogenic according to our data. Variant chr5-62361319-G-A is described in ClinVar as [Pathogenic]. Clinvar id is 65401.Status of the report is criteria_provided_single_submitter, 1 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
KIF2A | NM_001098511.3 | c.950G>A | p.Ser317Asn | missense_variant | 10/21 | ENST00000407818.8 | |
KIF2A | NM_004520.5 | c.950G>A | p.Ser317Asn | missense_variant | 10/20 | ||
KIF2A | NM_001243953.2 | c.893G>A | p.Ser298Asn | missense_variant | 10/20 | ||
KIF2A | NM_001243952.2 | c.869G>A | p.Ser290Asn | missense_variant | 11/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
KIF2A | ENST00000407818.8 | c.950G>A | p.Ser317Asn | missense_variant | 10/21 | 1 | NM_001098511.3 | A1 |
Frequencies
GnomAD3 genomes ? Cov.: 33
GnomAD3 genomes
?
Cov.:
33
GnomAD4 exome Cov.: 28
GnomAD4 exome
Cov.:
28
GnomAD4 genome ? Cov.: 33
GnomAD4 genome
?
Cov.:
33
ClinVar
Significance: Pathogenic
Submissions summary: Pathogenic:2
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
Complex cortical dysplasia with other brain malformations 3 Pathogenic:1
Pathogenic, no assertion criteria provided | literature only | OMIM | Jun 01, 2013 | - - |
not provided Pathogenic:1
Pathogenic, criteria provided, single submitter | clinical testing | Invitae | Nov 25, 2017 | This sequence change replaces serine with asparagine at codon 317 of the KIF2A protein (p.Ser317Asn). The serine residue is moderately conserved and there is a small physicochemical difference between serine and asparagine. This variant is not present in population databases (ExAC no frequency). This variant has been reported to be de novo in individuals affected with KIF2A-related disease (PMID: 27747449, 23603762). ClinVar contains an entry for this variant (Variation ID: 65401). Algorithms developed to predict the effect of missense changes on protein structure and function do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Possibly Damaging"; Align-GVGD: "Class C0"). For these reasons, this variant has been classified as Pathogenic. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Uncertain
T
BayesDel_noAF
Benign
Cadd
Pathogenic
Dann
Uncertain
DEOGEN2
Uncertain
D;.;.;.;T
Eigen
Pathogenic
Eigen_PC
Pathogenic
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D;T
M_CAP
Pathogenic
D
MetaRNN
Pathogenic
D;D;D;D;D
MetaSVM
Pathogenic
D
MutationAssessor
Pathogenic
H;.;H;.;.
MutationTaster
Benign
D;D;D;D
PrimateAI
Pathogenic
D
PROVEAN
Uncertain
D;D;D;D;N
REVEL
Uncertain
Sift
Uncertain
D;D;D;D;D
Sift4G
Pathogenic
D;D;D;D;T
Polyphen
D;.;D;.;.
Vest4
MutPred
Loss of glycosylation at S317 (P = 0.0049);.;Loss of glycosylation at S317 (P = 0.0049);.;.;
MVP
MPC
1.8
ClinPred
D
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
Name
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