13-52461541-A-G

Variant names:

• chr13-52461541-A-G
• rs368402985
• NM_018204.5:c.715A>G

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.715A>G​(p.Thr239Ala) 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. 13/22 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. T239P) 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: 1.43
• 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=0.12764758).

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.715A>G	p.Thr239Ala	missense	Exon 4 of 9	NP_060674.3
	CKAP2	NM_001098525.3		c.718A>G	p.Thr240Ala	missense	Exon 4 of 9	NP_001091995.1	Q8WWK9-1
	CKAP2	NM_001286686.2		c.571A>G	p.Thr191Ala	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.715A>G	p.Thr239Ala	missense	Exon 4 of 9	ENSP00000258607.5	Q8WWK9-5
	CKAP2	ENST00000378037.9	TSL:1	c.718A>G	p.Thr240Ala	missense	Exon 4 of 9	ENSP00000367276.4	Q8WWK9-1
	CKAP2	ENST00000378034.7	TSL:1	c.715A>G	p.Thr239Ala	missense	Exon 4 of 6	ENSP00000367273.2	Q8WWK9-4

Frequencies

GnomAD3 genomes Cov.: 30

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 30

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.076
BayesDel_addAF	Benign	-0.15	T
BayesDel_noAF	Benign	-0.46
CADD	Benign	11
DANN	Uncertain	0.99
DEOGEN2	Benign	0.20	T
Eigen	Benign	-0.18
Eigen_PC	Benign	-0.28
FATHMM_MKL	Benign	0.073	N
LIST_S2	Benign	0.43	T
M_CAP	Benign	0.0083	T
MetaRNN	Benign	0.13	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Uncertain	2.3	M
PhyloP100		1.4
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-2.2	N
REVEL	Benign	0.094
Sift	Benign	0.087	T
Sift4G	Benign	0.072	T
Polyphen		0.97	D
Vest4		0.045
MutPred		0.13		Loss of glycosylation at T239 (P = 0.0999)
MVP		0.26
MPC		0.31
ClinPred		0.63	D
GERP RS		5.4
Varity_R		0.13
gMVP		0.17
Mutation Taster		=90/10	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: rs368402985; hg19: chr13-53035676; COSMIC: COSV51624166; COSMIC: COSV51624166;