13-52455635-CGCGGTGGCGGTGGCGGTGGCGGTGGCGGTG-CGCGGTGGCGGTGGCGGTGGCGGTGGCGGTGGCGGTGGCGGTG

Variant names:

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

Variant summary

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

The NM_018204.5(CKAP2):​c.70+38_70+49dupTGGCGGTGGCGG variant causes a intron change. It is difficult to determine the true allele frequency of this variant because it is of type INS_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 0.00038 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00028 (0 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: Uncertain_significance. The variant received 0 ACMG points.

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+49dupTGGCGGTGGCGG		intron	N/A	NP_060674.3
	CKAP2	NM_001098525.3		c.70+38_70+49dupTGGCGGTGGCGG		intron	N/A	NP_001091995.1	Q8WWK9-1
	CKAP2	NM_001286687.2		c.70+38_70+49dupTGGCGGTGGCGG		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+9_70+10insGCGGTGGCGGTG		intron	N/A	ENSP00000258607.5	Q8WWK9-5
	CKAP2	ENST00000378037.9	TSL:1	c.70+9_70+10insGCGGTGGCGGTG		intron	N/A	ENSP00000367276.4	Q8WWK9-1
	CKAP2	ENST00000378034.7	TSL:1	c.70+9_70+10insGCGGTGGCGGTG		intron	N/A	ENSP00000367273.2	Q8WWK9-4

Frequencies

GnomAD3 genomes AF: 0.000376 AC: 57 AN: 151710 Hom.: 0 Cov.: 0

Gnomad AFR AF: 0.000654

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000656

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000581

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000383

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.000277 AC: 391 AN: 1411258 Hom.: 0 Cov.: 0 AF XY: 0.000275 AC XY: 193 AN XY: 701940

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR) AF: 0.000278 AC: 8 AN: 28796

American (AMR) AF: 0.000294 AC: 11 AN: 37358

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24570

East Asian (EAS) AF: 0.000117 AC: 4 AN: 34294

South Asian (SAS) AF: 0.000184 AC: 15 AN: 81414

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50898

Middle Eastern (MID) AF: 0.000198 AC: 1 AN: 5062

European-Non Finnish (NFE) AF: 0.000306 AC: 334 AN: 1091076

Other (OTH) AF: 0.000311 AC: 18 AN: 57790

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

GnomAD4 genome AF: 0.000382 AC: 58 AN: 151818 Hom.: 0 Cov.: 0 AF XY: 0.000270 AC XY: 20 AN XY: 74200

African (AFR) AF: 0.000676 AC: 28 AN: 41436

American (AMR) AF: 0.0000656 AC: 1 AN: 15254

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3462

East Asian (EAS) AF: 0.000583 AC: 3 AN: 5144

South Asian (SAS) AF: 0.00 AC: 0 AN: 4812

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10530

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 290

European-Non Finnish (NFE) AF: 0.000383 AC: 26 AN: 67876

Other (OTH) AF: 0.00 AC: 0 AN: 2106

Alfa AF: 0.0000714 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

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;