rs72652880

chr13-35862934-G-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BS1 BS2

The NM_001330071.2(DCLK1):c.940+8290C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0325 in 152,244 control chromosomes in the GnomAD database, including 140 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 0.033 (140 hom., cov: 33)
• Consequence: DCLK1 NM_001330071.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0970

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]

LOC105370163 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0325 (4950/152244) while in subpopulation NFE AF= 0.0501 (3405/68002). AF 95% confidence interval is 0.0487. There are 140 homozygotes in gnomad4. There are 2325 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High AC in GnomAd at 4951 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
DCLK1	NM_001330071.2	c.940+8290C>A		intron_variant		ENST00000360631.8
LOC105370163	XR_941855.3	n.82+4788G>T		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
DCLK1	ENST00000360631.8	c.940+8290C>A		intron_variant		5	NM_001330071.2	P3
DCLK1	ENST00000255448.8	c.940+8290C>A		intron_variant		1		A1
DCLK1	ENST00000379892.4	c.940+8290C>A		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.0325 AC: 4951 AN: 152126 Hom.: 141 Cov.: 33

Gnomad AFR AF: 0.00843

Gnomad AMI AF: 0.0362

Gnomad AMR AF: 0.0418

Gnomad ASJ AF: 0.0288

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00995

Gnomad FIN AF: 0.0250

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0501

Gnomad OTH AF: 0.0444

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.0325 AC: 4950 AN: 152244 Hom.: 140 Cov.: 33 AF XY: 0.0312 AC XY: 2325 AN XY: 74438

Gnomad4 AFR AF: 0.00840

Gnomad4 AMR AF: 0.0416

Gnomad4 ASJ AF: 0.0288

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.0102

Gnomad4 FIN AF: 0.0250

Gnomad4 NFE AF: 0.0501

Gnomad4 OTH AF: 0.0440

Alfa AF: 0.0363 Hom.: 23

Bravo AF: 0.0332

Asia WGS AF: 0.00577 AC: 20 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
Cadd	Benign	0.49
Dann	Benign	0.54

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: rs72652880; hg19: chr13-36437071;