rs147962548

Variant names:

• chr13-35854509-C-A
• rs147962548
• NM_001330071.2:c.1025G>T

Your query was ambiguous. Multiple possible variants found:

• chr13-35854509-C-A
• chr13-35854509-C-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BS2

The NM_001330071.2(DCLK1):​c.1025G>T​(p.Arg342Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000622 in 1,448,006 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R342Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000062 (0 hom.)
• Consequence: DCLK1 NM_001330071.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.56
• Publications: 0 publications found

Genes affected

DCLK1 (HGNC:2700): (doublecortin like kinase 1) 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. The encoded protein is involved in several different cellular processes, including neuronal migration, retrograde transport, neuronal apoptosis and neurogenesis. This gene is up-regulated by brain-derived neurotrophic factor and associated with memory and general cognitive abilities. Multiple transcript variants generated by two alternative promoter usage and alternative splicing have been reported, but the full-length nature and biological validity of some variants have not been defined. These variants encode different isoforms, which are differentially expressed and have different kinase activities.[provided by RefSeq, Sep 2010]

ACMG classification

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BS2: High AC in GnomAdExome4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.1025G>T	p.Arg342Leu	missense_variant	Exon 6 of 17	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.1025G>T	p.Arg342Leu	missense_variant	Exon 6 of 17	5	NM_001330071.2	ENSP00000353846.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.0000164 AC: 4 AN: 243330 AF XY: 0.0000228

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 FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000360

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000622 AC: 9 AN: 1448006 Hom.: 0 Cov.: 30 AF XY: 0.00000834 AC XY: 6 AN XY: 719758

African (AFR) AF: 0.00 AC: 0 AN: 33068

American (AMR) AF: 0.00 AC: 0 AN: 43404

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25738

East Asian (EAS) AF: 0.00 AC: 0 AN: 38912

South Asian (SAS) AF: 0.00 AC: 0 AN: 83790

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53104

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5694

European-Non Finnish (NFE) AF: 0.00000815 AC: 9 AN: 1104506

Other (OTH) AF: 0.00 AC: 0 AN: 59790

GnomAD4 genome Cov.: 33

Alfa AF: 0.0000450 Hom.: 0

Bravo AF: 0.0000113

ExAC AF: 0.0000165 AC: 2

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.30
BayesDel_addAF	Uncertain	0.10	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	.;T;.;.;.
Eigen	Uncertain	0.62
Eigen_PC	Pathogenic	0.67
FATHMM_MKL	Pathogenic	0.99	D
LIST_S2	Uncertain	0.97	D;D;D;D;D
M_CAP	Benign	0.022	T
MetaRNN	Uncertain	0.56	D;D;D;D;D
MetaSVM	Benign	-0.28	T
MutationAssessor	Uncertain	2.4	.;M;.;M;.
PhyloP100		6.6
PrimateAI	Pathogenic	0.84	D
PROVEAN	Uncertain	-2.5	.;D;N;N;D
REVEL	Benign	0.27
Sift	Uncertain	0.0040	.;D;D;D;D
Sift4G	Benign	0.073	T;T;T;D;D
Polyphen		0.79	P;.;P;P;.
Vest4		0.61
MutPred		0.29		.;Loss of MoRF binding (P = 0.0125);.;Loss of MoRF binding (P = 0.0125);Loss of MoRF binding (P = 0.0125);
MVP		0.78
MPC		2.0
ClinPred		0.62	D
GERP RS		5.7
Varity_R		0.40
gMVP		0.66
Mutation Taster		=53/47	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.070		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

dbSNP: rs147962548; hg19: chr13-36428646;