Genetic Variant CKAP2L:c.2013-426A>C (chr2-112739474-T-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_152515.5(CKAP2L):c.2013-426A>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.458 in 152,060 control chromosomes in the GnomAD database, including 15,929 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.46 ( 15929 hom., cov: 32)

Consequence

CKAP2L
NM_152515.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.142

Publications

4 publications found

Variant links:

Genes affected

CKAP2L (HGNC:26877): (cytoskeleton associated protein 2 like) The protein encoded by this gene is thought to be a mitotic spindle protein important to neural stem or progenitor cells. Mutations in this gene have been associated with spindle organization defects, including mitotic spindle defects, lagging chromosomes, and chromatin bridges. There is evidence that mutations in this gene are associated with Filippi syndrome, characterized by growth defects, microcephaly, intellectual disability, facial feature defects, and syndactyly. There is a pseudogene of this gene on chromosome 20. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Jan 2015]

CKAP2L links:

NT5DC4 (HGNC:27678): (5'-nucleotidase domain containing 4) Predicted to enable 5'-nucleotidase activity. Predicted to be involved in dephosphorylation. [provided by Alliance of Genome Resources, Apr 2022]

NT5DC4 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.493 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_152515.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CKAP2L	NM_152515.5	MANE Select	c.2013-426A>C	intron	N/A	NP_689728.3
CKAP2L	NM_001304361.2		c.1518-426A>C	intron	N/A	NP_001291290.1
NT5DC4	NM_001350494.2		c.1249-2938T>G	intron	N/A	NP_001337423.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein
CKAP2L	ENST00000302450.11	TSL:1 MANE Select	c.2013-426A>C	intron	N/A	ENSP00000305204.6
NT5DC4	ENST00000327581.4	TSL:1	c.1249-2938T>G	intron	N/A	ENSP00000330247.4
NT5DC4	ENST00000690591.1		c.1345-1046T>G	intron	N/A	ENSP00000508583.1

Frequencies

GnomAD3 genomes

AF:

0.458

AC:

69551

AN:

151942

Hom.:

15927

Cov.:

show subpopulations

Gnomad AFR

AF:

0.497

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.437

Gnomad ASJ

AF:

0.466

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.511

Gnomad FIN

AF:

0.421

Gnomad MID

AF:

0.576

Gnomad NFE

AF:

0.452

Gnomad OTH

AF:

0.446

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.458

AC:

69572

AN:

152060

Hom.:

15929

Cov.:

AF XY:

0.455

AC XY:

33846

AN XY:

74334

show subpopulations

African (AFR)

AF:

0.497

AC:

20575

AN:

41434

American (AMR)

AF:

0.437

AC:

6676

AN:

15274

Ashkenazi Jewish (ASJ)

AF:

0.466

AC:

1616

AN:

3468

East Asian (EAS)

AF:

0.307

AC:

1586

AN:

5168

South Asian (SAS)

AF:

0.510

AC:

2456

AN:

4818

European-Finnish (FIN)

AF:

0.421

AC:

4453

AN:

10580

Middle Eastern (MID)

AF:

0.578

AC:

170

AN:

294

European-Non Finnish (NFE)

AF:

0.451

AC:

30702

AN:

68002

Other (OTH)

AF:

0.442

AC:

933

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1949

3898

5847

7796

9745

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

642

1284

1926

2568

3210

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.463

Hom.:

2500

Bravo

AF:

0.454

Asia WGS

AF:

0.417

AC:

1449

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

8.1

(source)

DANN

Benign

0.73

PhyloP100

-0.14

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over