Genetic Variant DCLK3:p.Arg761Gln (chr3-36715500-C-T) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001394672.2(DCLK3):c.2282G>A(p.Arg761Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000797 in 1,531,516 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000059 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000082 ( 0 hom. )

Consequence

DCLK3
NM_001394672.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.456

Variant links:

Genes affected

DCLK3 (HGNC:19005): (doublecortin like kinase 3) Predicted to enable protein kinase activity. Predicted to be involved in peptidyl-serine phosphorylation. Predicted to act upstream of or within negative regulation of protein localization to nucleus. Predicted to be active in cytoplasm and nucleus. [provided by Alliance of Genome Resources, Apr 2022]

DCLK3 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.08502287).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK3	NM_001394672.2 link	c.2282G>A	p.Arg761Gln	missense_variant	Exon 5 of 5	ENST00000636136.2	NP_001381601.1
DCLK3	NM_033403.1 link	c.1775G>A	p.Arg592Gln	missense_variant	Exon 5 of 5		NP_208382.1	Q9C098B3KVM3
DCLK3	XM_047449090.1 link	c.2114G>A	p.Arg705Gln	missense_variant	Exon 4 of 4		XP_047305046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK3	ENST00000636136.2 link	c.2282G>A	p.Arg761Gln	missense_variant	Exon 5 of 5	5	NM_001394672.2	ENSP00000489900.1		A0A1B0GTZ4
DCLK3	ENST00000416516.2 link	c.1775G>A	p.Arg592Gln	missense_variant	Exon 5 of 5	5		ENSP00000394484.2		Q9C098

Frequencies

GnomAD3 genomes

AF:

0.0000591

AC:

AN:

152174

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

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:

0.000132

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000226

AC:

AN:

176622

Hom.:

AF XY:

0.0000105

AC XY:

AN XY:

95456

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000479

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000819

AC:

113

AN:

1379342

Hom.:

Cov.:

AF XY:

0.0000882

AC XY:

AN XY:

679956

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000137

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.000103

Gnomad4 OTH exome

AF:

0.0000176

GnomAD4 genome

AF:

0.0000591

AC:

AN:

152174

Hom.:

Cov.:

AF XY:

0.0000673

AC XY:

AN XY:

74334

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.00

Bravo

AF:

0.0000453

ExAC

AF:

0.0000249

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jun 22, 2021

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1775G>A (p.R592Q) alteration is located in exon 5 (coding exon 4) of the DCLK3 gene. This alteration results from a G to A substitution at nucleotide position 1775, causing the arginine (R) at amino acid position 592 to be replaced by a glutamine (Q). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.086

BayesDel_addAF

Benign

-0.27

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.13

LIST_S2

Uncertain

0.97

D;D

M_CAP

Benign

0.026

MetaRNN

Benign

0.085

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.48

N;.

PrimateAI

Benign

0.21

PROVEAN

Benign

-1.3

N;.

REVEL

Benign

0.055

Sift

Benign

0.11

T;.

Sift4G

Benign

0.12

T;.

Polyphen

0.54

P;.

Vest4

0.17

MutPred

0.52

Loss of MoRF binding (P = 0.0878);.;

MVP

0.73

MPC

0.27

ClinPred

0.090

GERP RS

1.7

Varity_R

0.077

gMVP

0.58

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

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