rs1958568988

Variant names:

• chr13-52461203-C-T
• rs1958568988
• NM_018204.5:c.377C>T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_018204.5(CKAP2):​c.377C>T​(p.Thr126Ile) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000958 in 1,461,656 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 30)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: CKAP2 NM_018204.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.229
• Publications: 0 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.042897433).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_018204.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKAP2	NM_018204.5	MANE Select	c.377C>T	p.Thr126Ile	missense	Exon 4 of 9	NP_060674.3
	CKAP2	NM_001098525.3		c.380C>T	p.Thr127Ile	missense	Exon 4 of 9	NP_001091995.1	Q8WWK9-1
	CKAP2	NM_001286686.2		c.233C>T	p.Thr78Ile	missense	Exon 4 of 9	NP_001273615.1	Q8WWK9-6

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKAP2	ENST00000258607.10	TSL:1 MANE Select	c.377C>T	p.Thr126Ile	missense	Exon 4 of 9	ENSP00000258607.5	Q8WWK9-5
	CKAP2	ENST00000378037.9	TSL:1	c.380C>T	p.Thr127Ile	missense	Exon 4 of 9	ENSP00000367276.4	Q8WWK9-1
	CKAP2	ENST00000378034.7	TSL:1	c.377C>T	p.Thr126Ile	missense	Exon 4 of 6	ENSP00000367273.2	Q8WWK9-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461656 Hom.: 0 Cov.: 32 AF XY: 0.00000825 AC XY: 6 AN XY: 727110

African (AFR) AF: 0.00 AC: 0 AN: 33472

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26122

East Asian (EAS) AF: 0.00 AC: 0 AN: 39684

South Asian (SAS) AF: 0.00 AC: 0 AN: 86154

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53418

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.0000108 AC: 12 AN: 1111952

Other (OTH) AF: 0.0000331 AC: 2 AN: 60386

GnomAD4 genome Cov.: 30

Alfa AF: 0.0000935 Hom.: 0

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.60
CADD	Benign	1.2
DANN	Benign	0.34
DEOGEN2	Benign	0.016	T
Eigen	Benign	-1.2
Eigen_PC	Benign	-1.3
FATHMM_MKL	Benign	0.066	N
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.0046	T
MetaRNN	Benign	0.043	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.46	N
PhyloP100		-0.23
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.025
Sift	Benign	0.26	T
Sift4G	Uncertain	0.019	D
Polyphen		0.42	B
Vest4		0.025
MutPred		0.19		Loss of glycosylation at T127 (P = 0.0296)
MVP		0.14
MPC		0.057
ClinPred		0.12	T
GERP RS		-0.95
Varity_R		0.021
gMVP		0.13
Mutation Taster		=97/3	polymorphism

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

Other links and lift over

dbSNP: rs1958568988; hg19: chr13-53035338;