Genetic Variant ENST00000460982:c.*159G>T (chr13-35850561-C-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000460982.1(DCLK1):c.*159G>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000018 in 1,109,974 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)

Exomes 𝑓: 0.0000018 ( 0 hom. )

Consequence

DCLK1
ENST00000460982.1 3_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.287

Publications

7 publications found

Variant links:

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]

DCLK1 links:

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ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000460982.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DCLK1	NM_001330071.2	MANE Select	c.1035+3938G>T	intron	N/A	NP_001317000.1	O15075-1
DCLK1	NM_001438021.1		c.*159G>T	3_prime_UTR	Exon 7 of 7	NP_001424950.1	Q5VZY9
DCLK1	NM_001195430.2		c.*159G>T	3_prime_UTR	Exon 3 of 3	NP_001182359.1	A0A9L9PXT2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
DCLK1	ENST00000460982.1	TSL:1	c.*159G>T	3_prime_UTR	Exon 3 of 3	ENSP00000516676.1	A0A9L9PXT2
DCLK1	ENST00000360631.8	TSL:5 MANE Select	c.1035+3938G>T	intron	N/A	ENSP00000353846.3	O15075-1
DCLK1	ENST00000255448.8	TSL:1	c.1035+3938G>T	intron	N/A	ENSP00000255448.4	O15075-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000180

AC:

AN:

1109974

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

527128

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

23098

American (AMR)

AF:

0.00

AC:

AN:

8824

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

14610

East Asian (EAS)

AF:

0.00

AC:

AN:

26540

South Asian (SAS)

AF:

0.00

AC:

AN:

25544

European-Finnish (FIN)

AF:

0.00

AC:

AN:

34316

Middle Eastern (MID)

AF:

0.00

AC:

AN:

3028

European-Non Finnish (NFE)

AF:

0.00000108

AC:

AN:

929536

Other (OTH)

AF:

0.0000225

AC:

AN:

44478

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

6212

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.45

(source)

DANN

Benign

0.46

PhyloP100

-0.29

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over