13-52455635-CGCGGTGGCGGTGGCGGTGGCGGTGGCGGTG-CGCGGTGGCGGTGGCGGTGGCGGTG

Variant names:

• chr13-52455635-CGCGGTG-C
• rs72440971
• NM_018204.5:c.70+44_70+49delTGGCGG

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_018204.5(CKAP2):​c.70+44_70+49delTGGCGG variant causes a intron change. The variant allele was found at a frequency of 0.0054 in 1,562,876 control chromosomes in the GnomAD database, including 109 homozygotes. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.015 (42 hom., cov: 0)
  • Exomes 𝑓: 0.0044 (67 hom.)
• Consequence: CKAP2 NM_018204.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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 -10 ACMG points.

• BP6: Variant 13-52455635-CGCGGTG-C is Benign according to our data. Variant chr13-52455635-CGCGGTG-C is described in ClinVar as Benign. ClinVar VariationId is 2037524.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.0151 (2297/151806) while in subpopulation AFR AF = 0.0407 (1684/41426). AF 95% confidence interval is 0.039. There are 42 homozygotes in GnomAd4. There are 1104 alleles in the male GnomAd4 subpopulation. Median coverage is 0. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 42 AR gene

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+44_70+49delTGGCGG		intron	N/A	NP_060674.3
	CKAP2	NM_001098525.3		c.70+44_70+49delTGGCGG		intron	N/A	NP_001091995.1	Q8WWK9-1
	CKAP2	NM_001286687.2		c.70+44_70+49delTGGCGG		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+15delGCGGTG		intron	N/A	ENSP00000258607.5	Q8WWK9-5
	CKAP2	ENST00000378037.9	TSL:1	c.70+10_70+15delGCGGTG		intron	N/A	ENSP00000367276.4	Q8WWK9-1
	CKAP2	ENST00000378034.7	TSL:1	c.70+10_70+15delGCGGTG		intron	N/A	ENSP00000367273.2	Q8WWK9-4

Frequencies

GnomAD3 genomes AF: 0.0151 AC: 2290 AN: 151698 Hom.: 42 Cov.: 0

Gnomad AFR AF: 0.0406

Gnomad AMI AF: 0.0826

Gnomad AMR AF: 0.00814

Gnomad ASJ AF: 0.00722

Gnomad EAS AF: 0.000969

Gnomad SAS AF: 0.0166

Gnomad FIN AF: 0.00218

Gnomad MID AF: 0.00962

Gnomad NFE AF: 0.00376

Gnomad OTH AF: 0.0115

GnomAD2 exomes AF: 0.00594 AC: 1106 AN: 186206 AF XY: 0.00667

Gnomad AFR exome AF: 0.0280

Gnomad AMR exome AF: 0.00401

Gnomad ASJ exome AF: 0.00549

Gnomad EAS exome AF: 0.000545

Gnomad FIN exome AF: 0.00302

Gnomad NFE exome AF: 0.00274

Gnomad OTH exome AF: 0.00571

GnomAD4 exome AF: 0.00435 AC: 6139 AN: 1411070 Hom.: 67 AF XY: 0.00475 AC XY: 3336 AN XY: 701802

African (AFR) AF: 0.0361 AC: 1040 AN: 28790

American (AMR) AF: 0.00525 AC: 196 AN: 37344

Ashkenazi Jewish (ASJ) AF: 0.00590 AC: 145 AN: 24566

East Asian (EAS) AF: 0.000671 AC: 23 AN: 34294

South Asian (SAS) AF: 0.0170 AC: 1379 AN: 81324

European-Finnish (FIN) AF: 0.00289 AC: 147 AN: 50892

Middle Eastern (MID) AF: 0.0196 AC: 99 AN: 5060

European-Non Finnish (NFE) AF: 0.00250 AC: 2727 AN: 1091036

Other (OTH) AF: 0.00663 AC: 383 AN: 57764

GnomAD4 genome AF: 0.0151 AC: 2297 AN: 151806 Hom.: 42 Cov.: 0 AF XY: 0.0149 AC XY: 1104 AN XY: 74196

African (AFR) AF: 0.0407 AC: 1684 AN: 41426

American (AMR) AF: 0.00813 AC: 124 AN: 15252

Ashkenazi Jewish (ASJ) AF: 0.00722 AC: 25 AN: 3462

East Asian (EAS) AF: 0.000972 AC: 5 AN: 5144

South Asian (SAS) AF: 0.0164 AC: 79 AN: 4812

European-Finnish (FIN) AF: 0.00218 AC: 23 AN: 10530

Middle Eastern (MID) AF: 0.0103 AC: 3 AN: 290

European-Non Finnish (NFE) AF: 0.00376 AC: 255 AN: 67876

Other (OTH) AF: 0.0114 AC: 24 AN: 2106

Alfa AF: 0.00421 Hom.: 1803

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

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;