3-36718013-C-A

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

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

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001394672.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK3	NM_001394672.2	MANE Select	c.2257G>T	p.Asp753Tyr	missense	Exon 4 of 5	NP_001381601.1	A0A1B0GTZ4
	DCLK3	NM_033403.1		c.1750G>T	p.Asp584Tyr	missense	Exon 4 of 5	NP_208382.1	Q9C098

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK3	ENST00000636136.2	TSL:5 MANE Select	c.2257G>T	p.Asp753Tyr	missense	Exon 4 of 5	ENSP00000489900.1	A0A1B0GTZ4
	DCLK3	ENST00000416516.2	TSL:5	c.1750G>T	p.Asp584Tyr	missense	Exon 4 of 5	ENSP00000394484.2	Q9C098
	DCLK3	ENST00000929032.1		c.2093-2492G>T		intron	N/A	ENSP00000599091.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Benign	0.055	D
MetaRNN	Uncertain	0.72	D
MetaSVM	Uncertain	-0.14	T
MutationAssessor	Benign	2.0	M
PhyloP100		6.1
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
Mutation Taster		=68/32	polymorphism

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

Other links and lift over

hg19: chr3-36759504;