chr13-35822777-C-T

Position:

• chr13-35822777-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Moderate BP6_Very_Strong BP7 BS2

The NM_001330071.2(DCLK1):​c.1506G>A​(p.Leu502Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00297 in 1,613,868 control chromosomes in the GnomAD database, including 52 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0031 (6 hom., cov: 31)
  • Exomes 𝑓: 0.0030 (46 hom.)
• Consequence: DCLK1 NM_001330071.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.47

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.36).
• BP6: Variant 13-35822777-C-T is Benign according to our data. Variant chr13-35822777-C-T is described in ClinVar as [Benign]. Clinvar id is 769396.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=1.47 with no splicing effect.
• BS2: High AC in GnomAd4 at 468 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.1506G>A	p.Leu502Leu	synonymous_variant	11/17	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.1506G>A	p.Leu502Leu	synonymous_variant	11/17	5	NM_001330071.2	ENSP00000353846.3
DCLK1	ENST00000255448.8	c.1506G>A	p.Leu502Leu	synonymous_variant	11/18	1		ENSP00000255448.4
DCLK1	ENST00000379893.5	c.585G>A	p.Leu195Leu	synonymous_variant	7/13	2		ENSP00000369223.1
DCLK1	ENST00000615680.5	c.585G>A	p.Leu195Leu	synonymous_variant	7/14	2		ENSP00000484452.1

Frequencies

GnomAD3 genomes AF: 0.00308 AC: 468 AN: 151874 Hom.: 6 Cov.: 31

Gnomad AFR AF: 0.000315

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00309

Gnomad ASJ AF: 0.0507

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.00710

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00949

Gnomad NFE AF: 0.00266

Gnomad OTH AF: 0.00624

GnomAD3 exomes AF: 0.00468 AC: 1177 AN: 251400 Hom.: 15 AF XY: 0.00494 AC XY: 671 AN XY: 135870

Gnomad AFR exome AF: 0.000431

Gnomad AMR exome AF: 0.00179

Gnomad ASJ exome AF: 0.0478

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00790

Gnomad FIN exome AF: 0.0000462

Gnomad NFE exome AF: 0.00309

Gnomad OTH exome AF: 0.00505

GnomAD4 exome AF: 0.00295 AC: 4318 AN: 1461876 Hom.: 46 Cov.: 32 AF XY: 0.00319 AC XY: 2320 AN XY: 727242

Gnomad4 AFR exome AF: 0.000627

Gnomad4 AMR exome AF: 0.00219

Gnomad4 ASJ exome AF: 0.0478

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00719

Gnomad4 FIN exome AF: 0.0000936

Gnomad4 NFE exome AF: 0.00169

Gnomad4 OTH exome AF: 0.00606

GnomAD4 genome AF: 0.00308 AC: 468 AN: 151992 Hom.: 6 Cov.: 31 AF XY: 0.00287 AC XY: 213 AN XY: 74298

Gnomad4 AFR AF: 0.000314

Gnomad4 AMR AF: 0.00308

Gnomad4 ASJ AF: 0.0507

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.00711

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00266

Gnomad4 OTH AF: 0.00618

Alfa AF: 0.00573 Hom.: 5

Bravo AF: 0.00322

Asia WGS AF: 0.00260 AC: 9 AN: 3478

EpiCase AF: 0.00480

EpiControl AF: 0.00522

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Aug 06, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.36
CADD	Benign	10
DANN	Benign	0.72

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: rs139958301; hg19: chr13-36396914;