Genetic Variant CKAP2:p.Thr142Pro (chr13-52461250-A-C) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

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

The NM_018204.5(CKAP2):c.424A>C(p.Thr142Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000149 in 1,613,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00012 ( 0 hom., cov: 30)

Exomes 𝑓: 0.00015 ( 0 hom. )

Consequence

CKAP2
NM_018204.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 1.25

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]

CKAP2 links:

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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=0.20142332).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKAP2	NM_018204.5 link	c.424A>C	p.Thr142Pro	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
CKAP2	ENST00000258607.10 link	c.424A>C	p.Thr142Pro	missense_variant	Exon 4 of 9	1	NM_018204.5	ENSP00000258607.5		Q8WWK9-5

Frequencies

GnomAD3 genomes

AF:

0.000125

AC:

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000279

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000918

AC:

AN:

250672

Hom.:

AF XY:

0.0000812

AC XY:

AN XY:

135432

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.000194

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.000152

AC:

222

AN:

1461242

Hom.:

Cov.:

AF XY:

0.000149

AC XY:

108

AN XY:

726862

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.0000187

Gnomad4 NFE exome

AF:

0.000198

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000125

AC:

AN:

152202

Hom.:

Cov.:

AF XY:

0.0000941

AC XY:

AN XY:

74352

show subpopulations

Gnomad4 AFR

AF:

0.00

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:

0.000279

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.000184

Hom.:

Bravo

AF:

0.000106

ExAC

AF:

0.0000412

AC:

EpiCase

AF:

0.00

EpiControl

AF:

0.000178

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

May 23, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.427A>C (p.T143P) alteration is located in exon 4 (coding exon 4) of the CKAP2 gene. This alteration results from a A to C substitution at nucleotide position 427, causing the threonine (T) at amino acid position 143 to be replaced by a proline (P). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.19

BayesDel_addAF

Benign

-0.19

BayesDel_noAF

Benign

-0.18

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.14

T;.;.;T;.;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.48

FATHMM_MKL

Uncertain

0.91

LIST_S2

Benign

0.65

T;T;T;T;T;T

M_CAP

Benign

0.011

MetaRNN

Benign

0.20

T;T;T;T;T;T

MetaSVM

Benign

-0.80

MutationAssessor

Uncertain

2.5

.;.;.;M;.;.

PrimateAI

Benign

0.34

PROVEAN

Pathogenic

-4.9

D;N;N;N;N;D

REVEL

Benign

0.15

Sift

Uncertain

0.0080

D;T;T;T;T;D

Sift4G

Pathogenic

0.0

D;D;D;D;D;D

Polyphen

1.0

.;.;.;D;.;.

Vest4

0.40, 0.36, 0.39, 0.36

MVP

0.41

MPC

0.36

ClinPred

0.52

GERP RS

4.1

Varity_R

0.15

gMVP

0.14

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over