Genetic Variant CKAP2:p.His260Tyr (chr13-52461604-C-T) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_018204.5(CKAP2):c.778C>T(p.His260Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000452 in 1,614,142 control chromosomes in the GnomAD database, including 4 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0024 ( 0 hom., cov: 31)

Exomes 𝑓: 0.00025 ( 4 hom. )

Consequence

CKAP2
NM_018204.5 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

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]

CKAP2 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.003535509).

BP6

Variant 13-52461604-C-T is Benign according to our data. Variant chr13-52461604-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 788446.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CKAP2	NM_018204.5 link	c.778C>T	p.His260Tyr	missense_variant	Exon 4 of 9	ENST00000258607.10	NP_060674.3	Q8WWK9-5

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
CKAP2	ENST00000258607.10 link	c.778C>T	p.His260Tyr	missense_variant	Exon 4 of 9	1	NM_018204.5	ENSP00000258607.5	Q8WWK9-5
CKAP2	ENST00000378037.9 link	c.781C>T	p.His261Tyr	missense_variant	Exon 4 of 9	1		ENSP00000367276.4	Q8WWK9-1
CKAP2	ENST00000378034.7 link	c.778C>T	p.His260Tyr	missense_variant	Exon 4 of 6	1		ENSP00000367273.2	Q8WWK9-4
CKAP2	ENST00000490903.5 link	c.634C>T	p.His212Tyr	missense_variant	Exon 4 of 9	2		ENSP00000417830.1	Q8WWK9-6

Frequencies

GnomAD3 genomes

AF:

0.00243

AC:

370

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00709

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00458

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000147

Gnomad OTH

AF:

0.00191

GnomAD3 exomes

AF:

0.000585

AC:

147

AN:

251380

Hom.:

AF XY:

0.000493

AC XY:

AN XY:

135858

show subpopulations

Gnomad AFR exome

AF:

0.00763

Gnomad AMR exome

AF:

0.000491

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:

0.00000880

Gnomad OTH exome

AF:

0.000816

GnomAD4 exome

AF:

0.000246

AC:

359

AN:

1461850

Hom.:

Cov.:

AF XY:

0.000212

AC XY:

154

AN XY:

727220

show subpopulations

Gnomad4 AFR exome

AF:

0.00747

Gnomad4 AMR exome

AF:

0.000939

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000108

Gnomad4 OTH exome

AF:

0.000911

GnomAD4 genome

AF:

0.00243

AC:

370

AN:

152292

Hom.:

Cov.:

AF XY:

0.00248

AC XY:

185

AN XY:

74458

show subpopulations

Gnomad4 AFR

AF:

0.00707

Gnomad4 AMR

AF:

0.00458

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000193

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000147

Gnomad4 OTH

AF:

0.00189

Alfa

AF:

0.000315

Hom.:

Bravo

AF:

0.00343

ESP6500AA

AF:

0.00681

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.000626

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.085

BayesDel_addAF

Benign

-0.58

BayesDel_noAF

Benign

-0.60

CADD

Benign

4.1

DANN

Benign

0.60

DEOGEN2

Benign

0.19

.;.;T;.

Eigen

Benign

-0.36

Eigen_PC

Benign

-0.41

FATHMM_MKL

Benign

0.041

LIST_S2

Benign

0.71

T;T;T;T

M_CAP

Benign

0.0025

MetaRNN

Benign

0.0035

T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

.;.;M;.

PrimateAI

Benign

0.28

PROVEAN

Benign

-1.5

N;N;N;N

REVEL

Benign

0.029

Sift

Benign

1.0

T;T;T;T

Sift4G

Benign

1.0

T;T;T;T

Polyphen

0.95

.;.;P;.

Vest4

0.12

MVP

0.29

MPC

0.073

ClinPred

0.19

GERP RS

3.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Varity_R

0.084

gMVP

0.27

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