rs144431404

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_018204.5(CKAP2):​c.778C>G​(p.His260Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,174 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. H260L) has been classified as Uncertain significance.

Frequency

Genomes: š‘“ 0.0000066 ( 0 hom., cov: 31)

Consequence

CKAP2
NM_018204.5 missense

Scores

3
16

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.215
Variant links:
Genes affected
CKAP2 (HGNC:1990): (cytoskeleton associated protein 2) This gene encodes a cytoskeleton-associated protein that stabalizes microtubules and plays a role in the regulation of cell division. The encoded protein is itself regulated through phosphorylation at multiple serine and threonine residues. There is a pseudogene of this gene on chromosome 14. Alternative splicing results in multiple transcript variations. [provided by RefSeq, Nov 2013]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.1145615).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CKAP2NM_018204.5 linkc.778C>G p.His260Asp missense_variant Exon 4 of 9 ENST00000258607.10 NP_060674.3 Q8WWK9-5

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CKAP2ENST00000258607.10 linkc.778C>G p.His260Asp missense_variant Exon 4 of 9 1 NM_018204.5 ENSP00000258607.5 Q8WWK9-5
CKAP2ENST00000378037.9 linkc.781C>G p.His261Asp missense_variant Exon 4 of 9 1 ENSP00000367276.4 Q8WWK9-1
CKAP2ENST00000378034.7 linkc.778C>G p.His260Asp missense_variant Exon 4 of 6 1 ENSP00000367273.2 Q8WWK9-4
CKAP2ENST00000490903.5 linkc.634C>G p.His212Asp missense_variant Exon 4 of 9 2 ENSP00000417830.1 Q8WWK9-6

Frequencies

GnomAD3 genomes
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
31
show subpopulations
Gnomad AFR
AF:
0.0000241
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00000398
AC:
1
AN:
251380
Hom.:
0
AF XY:
0.00000736
AC XY:
1
AN XY:
135858
show subpopulations
Gnomad AFR exome
AF:
0.0000615
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
Cov.:
32
GnomAD4 genome
AF:
0.00000657
AC:
1
AN:
152174
Hom.:
0
Cov.:
31
AF XY:
0.0000135
AC XY:
1
AN XY:
74330
show subpopulations
Gnomad4 AFR
AF:
0.0000241
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.00
Gnomad4 OTH
AF:
0.00
Bravo
AF:
0.0000113
ExAC
AF:
0.00000824
AC:
1

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.11
BayesDel_addAF
Benign
-0.33
T
BayesDel_noAF
Benign
-0.53
CADD
Benign
7.8
DANN
Uncertain
0.98
DEOGEN2
Benign
0.30
.;.;T;.
Eigen
Benign
-0.26
Eigen_PC
Benign
-0.35
FATHMM_MKL
Benign
0.087
N
LIST_S2
Benign
0.61
T;T;T;T
M_CAP
Benign
0.0077
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-1.0
T
MutationAssessor
Uncertain
2.6
.;.;M;.
PrimateAI
Benign
0.28
T
PROVEAN
Uncertain
-3.2
D;D;D;D
REVEL
Benign
0.042
Sift
Benign
0.21
T;T;T;T
Sift4G
Benign
0.20
T;T;T;T
Polyphen
0.76
.;.;P;.
Vest4
0.23
MutPred
0.26
.;.;Gain of relative solvent accessibility (P = 0.0249);.;
MVP
0.27
MPC
0.24
ClinPred
0.72
D
GERP RS
3.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.24
gMVP
0.33

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.0
Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs144431404; hg19: chr13-53035739; API