Genetic Variant NM_152515.5:c.2012+58G>A (chr2-112740760-C-T) – ACMG Classification: Benign (-20 pts)

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_152515.5(CKAP2L):c.2012+58G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0066 in 1,406,586 control chromosomes in the GnomAD database, including 496 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.033 ( 277 hom., cov: 32)

Exomes 𝑓: 0.0034 ( 219 hom. )

Consequence

CKAP2L
NM_152515.5 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.599

Publications

1 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:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

BP6

Variant 2-112740760-C-T is Benign according to our data. Variant chr2-112740760-C-T is described in ClinVar as Benign. ClinVar VariationId is 1277995.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 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	UniProt
CKAP2L	NM_152515.5	MANE Select	c.2012+58G>A	intron	N/A	NP_689728.3
CKAP2L	NM_001304361.2		c.1517+58G>A	intron	N/A	NP_001291290.1	Q8IYA6-3
NT5DC4	NM_001350494.2		c.1249-1652C>T	intron	N/A	NP_001337423.1	Q86YG4-1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
CKAP2L	ENST00000302450.11	TSL:1 MANE Select	c.2012+58G>A	intron	N/A	ENSP00000305204.6	Q8IYA6-1
NT5DC4	ENST00000327581.4	TSL:1	c.1249-1652C>T	intron	N/A	ENSP00000330247.4	Q86YG4-1
NT5DC4	ENST00000690591.1		c.*88C>T	3_prime_UTR	Exon 17 of 17	ENSP00000508583.1	A0A8I5KQQ4

Frequencies

GnomAD3 genomes

AF:

0.0327

AC:

4972

AN:

152110

Hom.:

275

Cov.:

show subpopulations

Gnomad AFR

AF:

0.114

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0114

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000829

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00949

Gnomad NFE

AF:

0.000235

Gnomad OTH

AF:

0.0220

GnomAD4 exome

AF:

0.00342

AC:

4296

AN:

1254358

Hom.:

219

AF XY:

0.00300

AC XY:

1872

AN XY:

623610

show subpopulations

African (AFR)

AF:

0.118

AC:

3397

AN:

28872

American (AMR)

AF:

0.00613

AC:

235

AN:

38328

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21522

East Asian (EAS)

AF:

0.00

AC:

AN:

38218

South Asian (SAS)

AF:

0.00185

AC:

135

AN:

73146

European-Finnish (FIN)

AF:

0.00

AC:

AN:

51048

Middle Eastern (MID)

AF:

0.00369

AC:

AN:

5152

European-Non Finnish (NFE)

AF:

0.0000910

AC:

AN:

945260

Other (OTH)

AF:

0.00803

AC:

424

AN:

52812

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.506

Heterozygous variant carriers

215

430

646

861

1076

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

102

204

306

408

510

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0328

AC:

4987

AN:

152228

Hom.:

277

Cov.:

AF XY:

0.0322

AC XY:

2395

AN XY:

74446

show subpopulations

African (AFR)

AF:

0.114

AC:

4744

AN:

41516

American (AMR)

AF:

0.0114

AC:

174

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3468

East Asian (EAS)

AF:

0.00

AC:

AN:

5186

South Asian (SAS)

AF:

0.000830

AC:

AN:

4822

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10612

Middle Eastern (MID)

AF:

0.0102

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000235

AC:

AN:

68024

Other (OTH)

AF:

0.0218

AC:

AN:

2110

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

230

459

689

918

1148

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

150

200

250

<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:

0.0343

Hom.:

Bravo

AF:

0.0375

Asia WGS

AF:

0.0100

AC:

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.66

(source)

DANN

Benign

0.60

PhyloP100

-0.60

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over