13-52455635-CGCGGTGGCGGTGGCGGTGGCGGTGGCGGTG-CGCGGTGGCGGTGGCGGTG

Variant names:

• chr13-52455635-CGCGGTGGCGGTG-C
• rs72440971
• NM_018204.5:c.70+38_70+49delTGGCGGTGGCGG

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_018204.5(CKAP2):​c.70+38_70+49delTGGCGGTGGCGG variant causes a intron change. The variant allele was found at a frequency of 0.0482 in 1,562,692 control chromosomes in the GnomAD database, including 2,273 homozygotes. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.054 (259 hom., cov: 0)
  • Exomes 𝑓: 0.048 (2014 hom.)
• Consequence: CKAP2 NM_018204.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 3.63
• 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]

CKAP2-DT (HGNC:56053): (CKAP2 divergent transcript)

ACMG classification

Our verdict: Benign. The variant received -8 ACMG points.

• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.0951 is higher than 0.05.

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.70+38_70+49delTGGCGGTGGCGG		intron	N/A	NP_060674.3
	CKAP2	NM_001098525.3		c.70+38_70+49delTGGCGGTGGCGG		intron	N/A	NP_001091995.1	Q8WWK9-1
	CKAP2	NM_001286687.2		c.70+38_70+49delTGGCGGTGGCGG		intron	N/A	NP_001273616.1	Q8WWK9-4

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CKAP2	ENST00000258607.10	TSL:1 MANE Select	c.70+10_70+21delGCGGTGGCGGTG		intron	N/A	ENSP00000258607.5	Q8WWK9-5
	CKAP2	ENST00000378037.9	TSL:1	c.70+10_70+21delGCGGTGGCGGTG		intron	N/A	ENSP00000367276.4	Q8WWK9-1
	CKAP2	ENST00000378034.7	TSL:1	c.70+10_70+21delGCGGTGGCGGTG		intron	N/A	ENSP00000367273.2	Q8WWK9-4

Frequencies

GnomAD3 genomes AF: 0.0540 AC: 8195 AN: 151698 Hom.: 260 Cov.: 0

Gnomad AFR AF: 0.0587

Gnomad AMI AF: 0.0551

Gnomad AMR AF: 0.0994

Gnomad ASJ AF: 0.0514

Gnomad EAS AF: 0.0171

Gnomad SAS AF: 0.0316

Gnomad FIN AF: 0.0480

Gnomad MID AF: 0.0641

Gnomad NFE AF: 0.0467

Gnomad OTH AF: 0.0441

GnomAD2 exomes AF: 0.0529 AC: 9857 AN: 186206 AF XY: 0.0478

Gnomad AFR exome AF: 0.0451

Gnomad AMR exome AF: 0.142

Gnomad ASJ exome AF: 0.0508

Gnomad EAS exome AF: 0.0134

Gnomad FIN exome AF: 0.0452

Gnomad NFE exome AF: 0.0420

Gnomad OTH exome AF: 0.0436

GnomAD4 exome AF: 0.0476 AC: 67130 AN: 1410886 Hom.: 2014 AF XY: 0.0467 AC XY: 32742 AN XY: 701714

African (AFR) AF: 0.0606 AC: 1744 AN: 28792

American (AMR) AF: 0.135 AC: 5043 AN: 37276

Ashkenazi Jewish (ASJ) AF: 0.0519 AC: 1275 AN: 24554

East Asian (EAS) AF: 0.0221 AC: 756 AN: 34282

South Asian (SAS) AF: 0.0322 AC: 2618 AN: 81388

European-Finnish (FIN) AF: 0.0444 AC: 2261 AN: 50890

Middle Eastern (MID) AF: 0.0306 AC: 155 AN: 5060

European-Non Finnish (NFE) AF: 0.0465 AC: 50705 AN: 1090874

Other (OTH) AF: 0.0445 AC: 2573 AN: 57770

GnomAD4 genome AF: 0.0540 AC: 8204 AN: 151806 Hom.: 259 Cov.: 0 AF XY: 0.0552 AC XY: 4095 AN XY: 74194

African (AFR) AF: 0.0587 AC: 2434 AN: 41436

American (AMR) AF: 0.0993 AC: 1514 AN: 15250

Ashkenazi Jewish (ASJ) AF: 0.0514 AC: 178 AN: 3462

East Asian (EAS) AF: 0.0169 AC: 87 AN: 5144

South Asian (SAS) AF: 0.0318 AC: 153 AN: 4810

European-Finnish (FIN) AF: 0.0480 AC: 505 AN: 10530

Middle Eastern (MID) AF: 0.0690 AC: 20 AN: 290

European-Non Finnish (NFE) AF: 0.0467 AC: 3170 AN: 67870

Other (OTH) AF: 0.0442 AC: 93 AN: 2106

Alfa AF: 0.0390 Hom.: 1803

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		3.6
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs72440971; hg19: chr13-53029770;