NM_001330071.2:c.1248T>C

Variant names:

• chr13-35828289-A-G
• rs2296645
• NM_001330071.2:c.1248T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BA1

The NM_001330071.2(DCLK1):​c.1248T>C​(p.Tyr416Tyr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.453 in 1,605,488 control chromosomes in the GnomAD database, including 171,032 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.38 (12870 hom., cov: 32)
  • Exomes 𝑓: 0.46 (158162 hom.)
• Consequence: DCLK1 NM_001330071.2 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 1.79
• Publications: 21 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.47).
• BP7: Synonymous conserved (PhyloP=1.79 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.474 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.1248T>C	p.Tyr416Tyr	synonymous_variant	Exon 9 of 17	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.1248T>C	p.Tyr416Tyr	synonymous_variant	Exon 9 of 17	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.1248T>C	p.Tyr416Tyr	synonymous_variant	Exon 9 of 18	1		ENSP00000255448.4
DCLK1	ENST00000379893.5	c.327T>C	p.Tyr109Tyr	synonymous_variant	Exon 5 of 13	2		ENSP00000369223.1
DCLK1	ENST00000615680.5	c.327T>C	p.Tyr109Tyr	synonymous_variant	Exon 5 of 14	2		ENSP00000484452.1

Frequencies

GnomAD3 genomes AF: 0.380 AC: 57665 AN: 151922 Hom.: 12868 Cov.: 32

Gnomad AFR AF: 0.140

Gnomad AMI AF: 0.587

Gnomad AMR AF: 0.397

Gnomad ASJ AF: 0.530

Gnomad EAS AF: 0.291

Gnomad SAS AF: 0.476

Gnomad FIN AF: 0.575

Gnomad MID AF: 0.513

Gnomad NFE AF: 0.479

Gnomad OTH AF: 0.428

GnomAD2 exomes AF: 0.436 AC: 107950 AN: 247372 AF XY: 0.447

Gnomad AFR exome AF: 0.129

Gnomad AMR exome AF: 0.376

Gnomad ASJ exome AF: 0.532

Gnomad EAS exome AF: 0.287

Gnomad FIN exome AF: 0.558

Gnomad NFE exome AF: 0.485

Gnomad OTH exome AF: 0.483

GnomAD4 exome AF: 0.461 AC: 669333 AN: 1453448 Hom.: 158162 Cov.: 33 AF XY: 0.463 AC XY: 335065 AN XY: 723314

African (AFR) AF: 0.131 AC: 4381 AN: 33404

American (AMR) AF: 0.378 AC: 16823 AN: 44528

Ashkenazi Jewish (ASJ) AF: 0.520 AC: 13553 AN: 26042

East Asian (EAS) AF: 0.305 AC: 12076 AN: 39560

South Asian (SAS) AF: 0.460 AC: 39488 AN: 85772

European-Finnish (FIN) AF: 0.549 AC: 27421 AN: 49946

Middle Eastern (MID) AF: 0.511 AC: 2910 AN: 5698

European-Non Finnish (NFE) AF: 0.474 AC: 525457 AN: 1108316

Other (OTH) AF: 0.452 AC: 27224 AN: 60182

GnomAD4 genome AF: 0.379 AC: 57667 AN: 152040 Hom.: 12870 Cov.: 32 AF XY: 0.385 AC XY: 28625 AN XY: 74302

African (AFR) AF: 0.140 AC: 5808 AN: 41518

American (AMR) AF: 0.397 AC: 6060 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.530 AC: 1837 AN: 3464

East Asian (EAS) AF: 0.291 AC: 1505 AN: 5174

South Asian (SAS) AF: 0.475 AC: 2293 AN: 4826

European-Finnish (FIN) AF: 0.575 AC: 6052 AN: 10530

Middle Eastern (MID) AF: 0.507 AC: 149 AN: 294

European-Non Finnish (NFE) AF: 0.479 AC: 32518 AN: 67952

Other (OTH) AF: 0.432 AC: 911 AN: 2110

Alfa AF: 0.457 Hom.: 18951

Bravo AF: 0.353

Asia WGS AF: 0.404 AC: 1405 AN: 3476

EpiCase AF: 0.487

EpiControl AF: 0.486

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.47
CADD	Benign	7.3
DANN	Benign	0.64
PhyloP100		1.8
Mutation Taster		=99/1	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
Splicevardb		2.0
SpliceAI score (max)		0.020		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: rs2296645; hg19: chr13-36402426; COSMIC: COSV55172314;