NM_001394672.2:c.2257G>T

Variant names:

• chr3-36718013-C-A
• NM_001394672.2:c.2257G>T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001394672.2(DCLK3):​c.2257G>T​(p.Asp753Tyr) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: DCLK3 NM_001394672.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.08

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK3	NM_001394672.2	c.2257G>T	p.Asp753Tyr	missense_variant	Exon 4 of 5	ENST00000636136.2	NP_001381601.1
DCLK3	NM_033403.1	c.1750G>T	p.Asp584Tyr	missense_variant	Exon 4 of 5		NP_208382.1
DCLK3	XM_047449090.1	c.2093-2492G>T		intron_variant	Intron 3 of 3		XP_047305046.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK3	ENST00000636136.2	c.2257G>T	p.Asp753Tyr	missense_variant	Exon 4 of 5	5	NM_001394672.2	ENSP00000489900.1
DCLK3	ENST00000416516.2	c.1750G>T	p.Asp584Tyr	missense_variant	Exon 4 of 5	5		ENSP00000394484.2
DCLK3	ENST00000498047.1	n.*80G>T		downstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Mar 07, 2025

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.1750G>T (p.D584Y) alteration is located in exon 4 (coding exon 3) of the DCLK3 gene. This alteration results from a G to T substitution at nucleotide position 1750, causing the aspartic acid (D) at amino acid position 584 to be replaced by a tyrosine (Y). 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	0.18
BayesDel_addAF	Uncertain	0.041	T
BayesDel_noAF	Benign	-0.18
CADD	Uncertain	25
DANN	Uncertain	0.99
DEOGEN2	Benign	0.11	T;.
Eigen	Pathogenic	0.75
Eigen_PC	Pathogenic	0.75
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.91	D;D
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.72	D;D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	2.0	M;.
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-6.1	D;.
REVEL	Uncertain	0.36
Sift	Uncertain	0.0020	D;.
Sift4G	Uncertain	0.0080	D;.
Polyphen		0.99	D;.
Vest4		0.57
MutPred		0.49		Loss of ubiquitination at K587 (P = 0.063);.;
MVP		0.88
MPC		0.50
ClinPred		0.96	D
GERP RS		5.5
Varity_R		0.74
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr3-36759504;