13-52461466-G-C

Variant names:

• chr13-52461466-G-C
• rs765437565
• NM_018204.5:c.640G>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_018204.5(CKAP2):​c.640G>C​(p.Ala214Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/22 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. A214S) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 30)
• Consequence: CKAP2 NM_018204.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.36
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.12310889).

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.640G>C	p.Ala214Pro	missense	Exon 4 of 9	NP_060674.3
	CKAP2	NM_001098525.3		c.643G>C	p.Ala215Pro	missense	Exon 4 of 9	NP_001091995.1	Q8WWK9-1
	CKAP2	NM_001286686.2		c.496G>C	p.Ala166Pro	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.640G>C	p.Ala214Pro	missense	Exon 4 of 9	ENSP00000258607.5	Q8WWK9-5
	CKAP2	ENST00000378037.9	TSL:1	c.643G>C	p.Ala215Pro	missense	Exon 4 of 9	ENSP00000367276.4	Q8WWK9-1
	CKAP2	ENST00000378034.7	TSL:1	c.640G>C	p.Ala214Pro	missense	Exon 4 of 6	ENSP00000367273.2	Q8WWK9-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

Alfa AF: 0.00 Hom.: 0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.12	T
BayesDel_noAF	Benign	-0.41
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.073
Eigen_PC	Benign	-0.16
FATHMM_MKL	Benign	0.56	D
LIST_S2	Benign	0.68	T
M_CAP	Benign	0.0053	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Uncertain	2.7	M
PhyloP100		1.4
PrimateAI	Benign	0.29	T
PROVEAN	Benign	-1.8	N
REVEL	Benign	0.10
Sift	Benign	0.12	T
Sift4G	Benign	0.20	T
Polyphen		1.0	D
Vest4		0.11
MutPred		0.30		Gain of relative solvent accessibility (P = 0.005)
MVP		0.26
MPC		0.072
ClinPred		0.35	T
GERP RS		4.7
Varity_R		0.39
gMVP		0.21
Mutation Taster		=74/26	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: rs765437565; hg19: chr13-53035601;