NM_001040260.4:c.14G>A

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001040260.4(DCLK2):c.14G>A(p.Arg5Lys) variant causes a missense change. The variant allele was found at a frequency of 0.0000227 in 1,543,156 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00014 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000093 ( 0 hom. )

Consequence

DCLK2
NM_001040260.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.07

Publications

3 publications found

Variant links:

Genes affected

DCLK2 (HGNC:19002): (doublecortin like kinase 2) This gene encodes a member of the protein kinase superfamily and the doublecortin family. The protein encoded by this gene contains two N-terminal doublecortin domains, which bind microtubules and regulate microtubule polymerization, a C-terminal serine/threonine protein kinase domain, which shows substantial homology to Ca2+/calmodulin-dependent protein kinase, and a serine/proline-rich domain in between the doublecortin and the protein kinase domains, which mediates multiple protein-protein interactions. The microtubule-polymerizing activity of the encoded protein is independent of its protein kinase activity. Mouse studies show that the DCX gene, another family member, and this gene share function in the establishment of hippocampal organization and that their absence results in a severe epileptic phenotype and lethality, as described in human patients with lissencephaly. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Sep 2010]

DCLK2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.12376657).

BS2

High AC in GnomAd4 at 22 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCLK2	NM_001040260.4	MANE Select	c.14G>A	p.Arg5Lys	missense	Exon 1 of 16	NP_001035350.2	Q8N568-1
DCLK2	NM_001040261.5		c.14G>A	p.Arg5Lys	missense	Exon 1 of 17	NP_001035351.4	Q8N568-3
DCLK2	NM_001410852.1		c.14G>A	p.Arg5Lys	missense	Exon 1 of 16	NP_001397781.1	Q8N568-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
DCLK2	ENST00000296550.12	TSL:1 MANE Select	c.14G>A	p.Arg5Lys	missense	Exon 1 of 16	ENSP00000296550.7	Q8N568-1
DCLK2	ENST00000302176.8	TSL:1	c.14G>A	p.Arg5Lys	missense	Exon 1 of 17	ENSP00000303887.8	Q8N568-3
DCLK2	ENST00000411937.6	TSL:1	n.14G>A		non_coding_transcript_exon	Exon 1 of 17	ENSP00000401916.2	G5E9L9

Frequencies

GnomAD3 genomes

AF:

0.000145

AC:

AN:

152090

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000459

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000384

AC:

AN:

182416

AF XY:

0.0000408

show subpopulations

Gnomad AFR exome

AF:

0.000292

Gnomad AMR exome

AF:

0.0000841

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000116

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000935

AC:

AN:

1391066

Hom.:

Cov.:

AF XY:

0.0000131

AC XY:

AN XY:

685888

show subpopulations

African (AFR)

AF:

0.000227

AC:

AN:

30776

American (AMR)

AF:

0.0000610

AC:

AN:

32768

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

21046

East Asian (EAS)

AF:

0.00

AC:

AN:

39146

South Asian (SAS)

AF:

0.00

AC:

AN:

73166

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49524

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5396

European-Non Finnish (NFE)

AF:

9.24e-7

AC:

AN:

1082048

Other (OTH)

AF:

0.0000525

AC:

AN:

57196

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<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:

0.000145

AC:

AN:

152090

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74302

show subpopulations

African (AFR)

AF:

0.000459

AC:

AN:

41428

American (AMR)

AF:

0.00

AC:

AN:

15284

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5138

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10610

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68022

Other (OTH)

AF:

0.00

AC:

AN:

2088

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.493

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000264

Hom.:

Bravo

AF:

0.000106

ExAC

AF:

0.0000332

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.21

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.19

CADD

Uncertain

(source)

DANN

Uncertain

0.99

DEOGEN2

Benign

0.0079

Eigen

Benign

0.16

Eigen_PC

Uncertain

0.28

FATHMM_MKL

Uncertain

0.88

LIST_S2

Benign

0.82

M_CAP

Benign

0.044

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.46

MutationAssessor

Uncertain

2.1

PhyloP100

4.1

PrimateAI

Pathogenic

0.84

PROVEAN

Benign

-0.46

REVEL

Benign

0.16

Sift

Benign

0.080

Sift4G

Benign

0.13

Polyphen

0.12

Vest4

0.27

MVP

0.73

MPC

0.33

ClinPred

0.046

GERP RS

4.5

PromoterAI

0.014

Neutral

(source)

Varity_R

0.32

gMVP

0.55

Mutation Taster

=58/42

polymorphism

(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