dbSNP rs6712572: CKAP2L:c.38-532C>A (chr2-112763101-G-T) – 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.38-532C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.596 in 152,058 control chromosomes in the GnomAD database, including 29,413 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 0.60 ( 29413 hom., cov: 32)

Consequence

CKAP2L
NM_152515.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.628

Publications

10 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 Gene-Disease associations (from GenCC):

Filippi syndrome
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P

CKAP2L links:

ENSG00000299339 (HGNC:):

ENSG00000299339 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=-1.02).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.869 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	Exon rank	MANE	Protein	UniProt
CKAP2L	NM_152515.5 link	c.38-532C>A	intron_variant	Intron 1 of 8	ENST00000302450.11	NP_689728.3	Q8IYA6-1
CKAP2L	NM_001304361.2 link	c.-399-532C>A	intron_variant	Intron 1 of 8		NP_001291290.1	Q8IYA6-3
CKAP2L	NR_130712.2 link	n.49-532C>A	intron_variant	Intron 1 of 9
CKAP2L	XM_011510666.3 link	c.-392+1461C>A	intron_variant	Intron 1 of 7		XP_011508968.1	Q8IYA6-3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CKAP2L	ENST00000302450.11 link	c.38-532C>A		intron_variant	Intron 1 of 8	1	NM_152515.5	ENSP00000305204.6		Q8IYA6-1

Frequencies

GnomAD3 genomes

AF:

0.596

AC:

90552

AN:

151940

Hom.:

29368

Cov.:

show subpopulations

Gnomad AFR

AF:

0.876

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.511

Gnomad ASJ

AF:

0.506

Gnomad EAS

AF:

0.308

Gnomad SAS

AF:

0.535

Gnomad FIN

AF:

0.439

Gnomad MID

AF:

0.655

Gnomad NFE

AF:

0.502

Gnomad OTH

AF:

0.576

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

GnomAD4 genome

AF:

0.596

AC:

90637

AN:

152058

Hom.:

29413

Cov.:

AF XY:

0.589

AC XY:

43773

AN XY:

74326

show subpopulations

African (AFR)

AF:

0.876

AC:

36381

AN:

41518

American (AMR)

AF:

0.510

AC:

7795

AN:

15278

Ashkenazi Jewish (ASJ)

AF:

0.506

AC:

1757

AN:

3472

East Asian (EAS)

AF:

0.307

AC:

1589

AN:

5176

South Asian (SAS)

AF:

0.535

AC:

2578

AN:

4822

European-Finnish (FIN)

AF:

0.439

AC:

4630

AN:

10540

Middle Eastern (MID)

AF:

0.656

AC:

193

AN:

294

European-Non Finnish (NFE)

AF:

0.502

AC:

34107

AN:

67942

Other (OTH)

AF:

0.570

AC:

1200

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1624

3248

4873

6497

8121

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

722

1444

2166

2888

3610

<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:

0.561

Hom.:

3162

Bravo

AF:

0.609

Asia WGS

AF:

0.445

AC:

1548

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

1.5

(source)

DANN

Benign

0.39

PhyloP100

-0.63

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over