13-35822831-G-A

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_Strong BP6_Moderate BP7 BS2

The NM_001330071.2(DCLK1):c.1452C>T(p.Thr484=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000759 in 1,613,710 control chromosomes in the GnomAD database, including 8 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (3 hom., cov: 31)
  • Exomes 𝑓: 0.00045 (5 hom.)
• Consequence: DCLK1 NM_001330071.2 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.58

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

Verdict is Benign. Variant got -11 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BP6: Variant 13-35822831-G-A is Benign according to our data. Variant chr13-35822831-G-A is described in ClinVar as [Benign]. Clinvar id is 732329.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-1.59 with no splicing effect.
• BS2: High AC in GnomAd at 563 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLK1	NM_001330071.2	c.1452C>T	p.Thr484=	synonymous_variant	11/17	ENST00000360631.8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLK1	ENST00000360631.8	c.1452C>T	p.Thr484=	synonymous_variant	11/17	5	NM_001330071.2	P3
DCLK1	ENST00000255448.8	c.1452C>T	p.Thr484=	synonymous_variant	11/18	1		A1
DCLK1	ENST00000379893.5	c.531C>T	p.Thr177=	synonymous_variant	7/13	2
DCLK1	ENST00000615680.5	c.531C>T	p.Thr177=	synonymous_variant	7/14	2

Frequencies

GnomAD3 genomes AF: 0.00371 AC: 563 AN: 151724 Hom.: 3 Cov.: 31

Gnomad AFR AF: 0.0124

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00158

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000209

Gnomad FIN AF: 0.000757

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000103

Gnomad OTH AF: 0.00482

GnomAD3 exomes AF: 0.00106 AC: 266 AN: 251380 Hom.: 3 AF XY: 0.000795 AC XY: 108 AN XY: 135858

Gnomad AFR exome AF: 0.0119

Gnomad AMR exome AF: 0.000896

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000131

Gnomad FIN exome AF: 0.00153

Gnomad NFE exome AF: 0.0000176

Gnomad OTH exome AF: 0.000326

GnomAD4 exome AF: 0.000453 AC: 662 AN: 1461868 Hom.: 5 Cov.: 32 AF XY: 0.000396 AC XY: 288 AN XY: 727242

Gnomad4 AFR exome AF: 0.0131

Gnomad4 AMR exome AF: 0.00101

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0000927

Gnomad4 FIN exome AF: 0.00144

Gnomad4 NFE exome AF: 0.0000288

Gnomad4 OTH exome AF: 0.000894

GnomAD4 genome AF: 0.00371 AC: 563 AN: 151842 Hom.: 3 Cov.: 31 AF XY: 0.00340 AC XY: 252 AN XY: 74214

Gnomad4 AFR AF: 0.0124

Gnomad4 AMR AF: 0.00158

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000210

Gnomad4 FIN AF: 0.000757

Gnomad4 NFE AF: 0.000103

Gnomad4 OTH AF: 0.00477

Alfa AF: 0.00161 Hom.: 1

Bravo AF: 0.00399

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jun 18, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.037
Dann	Benign	0.44

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

Other links and lift over

dbSNP: rs143725017; hg19: chr13-36396968;