Genetic Variant CKAP2:c.70+44_70+49delTGGCGG (chr13-52455635-CGCGGTG-C) – ACMG Classification: Benign (-10 pts)

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBS1BS2

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

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.63

Variant links:

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 links:

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

CKAP2-DT links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id 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 male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 42 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CKAP2	NM_018204.5 link	c.70+44_70+49delTGGCGG	intron_variant	Intron 1 of 8	ENST00000258607.10	NP_060674.3	Q8WWK9-5
CKAP2	NM_001098525.3 link	c.70+44_70+49delTGGCGG	intron_variant	Intron 1 of 8		NP_001091995.1	Q8WWK9-1
CKAP2	NM_001286687.2 link	c.70+44_70+49delTGGCGG	intron_variant	Intron 1 of 5		NP_001273616.1	Q8WWK9-4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKAP2	ENST00000258607.10 link	c.70+10_70+15delGCGGTG		intron_variant	Intron 1 of 8	1	NM_018204.5	ENSP00000258607.5		Q8WWK9-5

Frequencies

GnomAD3 genomes

AF:

0.0151

AC:

2290

AN:

151698

Hom.:

Cov.:

show subpopulations

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

GnomAD3 exomes

AF:

0.00594

AC:

1106

AN:

186206

Hom.:

AF XY:

0.00667

AC XY:

703

AN XY:

105348

show subpopulations

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 SAS exome

AF:

0.0162

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.:

AF XY:

0.00475

AC XY:

3336

AN XY:

701802

show subpopulations

Gnomad4 AFR exome

AF:

0.0361

Gnomad4 AMR exome

AF:

0.00525

Gnomad4 ASJ exome

AF:

0.00590

Gnomad4 EAS exome

AF:

0.000671

Gnomad4 SAS exome

AF:

0.0170

Gnomad4 FIN exome

AF:

0.00289

Gnomad4 NFE exome

AF:

0.00250

Gnomad4 OTH exome

AF:

0.00663

GnomAD4 genome

AF:

0.0151

AC:

2297

AN:

151806

Hom.:

Cov.:

AF XY:

0.0149

AC XY:

1104

AN XY:

74196

show subpopulations

Gnomad4 AFR

AF:

0.0407

Gnomad4 AMR

AF:

0.00813

Gnomad4 ASJ

AF:

0.00722

Gnomad4 EAS

AF:

0.000972

Gnomad4 SAS

AF:

0.0164

Gnomad4 FIN

AF:

0.00218

Gnomad4 NFE

AF:

0.00376

Gnomad4 OTH

AF:

0.0114

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 16, 2022

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over