rs149254206

Variant names:

• chr13-52461343-C-T
• rs149254206
• NM_018204.5:c.517C>T

Your query was ambiguous. Multiple possible variants found:

• chr13-52461343-C-T
• chr13-52461343-C-G

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_018204.5(CKAP2):​c.517C>T​(p.Pro173Ser) variant causes a missense change. The variant allele was found at a frequency of 0.0000558 in 1,614,130 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. P173R) has been classified as Uncertain significance.

• Frequency:
  • Genomes: 𝑓 0.00022 (0 hom., cov: 30)
  • Exomes 𝑓: 0.000039 (1 hom.)
• Consequence: CKAP2 NM_018204.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.64
• Publications: 2 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 -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.018737733).

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.517C>T	p.Pro173Ser	missense	Exon 4 of 9	NP_060674.3
	CKAP2	NM_001098525.3		c.520C>T	p.Pro174Ser	missense	Exon 4 of 9	NP_001091995.1	Q8WWK9-1
	CKAP2	NM_001286686.2		c.373C>T	p.Pro125Ser	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.517C>T	p.Pro173Ser	missense	Exon 4 of 9	ENSP00000258607.5	Q8WWK9-5
	CKAP2	ENST00000378037.9	TSL:1	c.520C>T	p.Pro174Ser	missense	Exon 4 of 9	ENSP00000367276.4	Q8WWK9-1
	CKAP2	ENST00000378034.7	TSL:1	c.517C>T	p.Pro173Ser	missense	Exon 4 of 6	ENSP00000367273.2	Q8WWK9-4

Frequencies

GnomAD3 genomes AF: 0.000217 AC: 33 AN: 152140 Hom.: 0 Cov.: 30

Gnomad AFR AF: 0.000772

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000655

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

GnomAD2 exomes AF: 0.0000796 AC: 20 AN: 251382 AF XY: 0.0000883

Gnomad AFR exome AF: 0.000923

Gnomad AMR exome AF: 0.0000867

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.000163

GnomAD4 exome AF: 0.0000390 AC: 57 AN: 1461872 Hom.: 1 Cov.: 32 AF XY: 0.0000413 AC XY: 30 AN XY: 727234

African (AFR) AF: 0.00140 AC: 47 AN: 33478

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26132

East Asian (EAS) AF: 0.00 AC: 0 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53420

Middle Eastern (MID) AF: 0.000347 AC: 2 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1112008

Other (OTH) AF: 0.0000662 AC: 4 AN: 60394

GnomAD4 genome AF: 0.000217 AC: 33 AN: 152258 Hom.: 0 Cov.: 30 AF XY: 0.000228 AC XY: 17 AN XY: 74440

African (AFR) AF: 0.000770 AC: 32 AN: 41554

American (AMR) AF: 0.0000654 AC: 1 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5184

South Asian (SAS) AF: 0.00 AC: 0 AN: 4826

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10604

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 68014

Other (OTH) AF: 0.00 AC: 0 AN: 2112

Alfa AF: 0.0000181 Hom.: 0

Bravo AF: 0.000298

ESP6500AA AF: 0.000681 AC: 3

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.0000906 AC: 11

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	0.15
BayesDel_addAF	Benign	-0.47	T
BayesDel_noAF	Benign	-0.52
CADD	Benign	20
DANN	Uncertain	0.99
DEOGEN2	Benign	0.12	T
Eigen	Benign	0.0038
Eigen_PC	Benign	0.12
FATHMM_MKL	Uncertain	0.89	D
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0065	T
MetaRNN	Benign	0.019	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		3.6
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.031
Sift	Benign	0.53	T
Sift4G	Benign	0.23	T
Polyphen		0.11	B
Vest4		0.22
MVP		0.32
MPC		0.077
ClinPred		0.048	T
GERP RS		4.5
Varity_R		0.065
gMVP		0.13
Mutation Taster		=89/11	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: rs149254206; hg19: chr13-53035478;