NM_001330071.2:c.1880T>C
Variant names:
Variant summary
Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.
The NM_001330071.2(DCLK1):c.1880T>C(p.Met627Thr) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00000434 in 1,613,704 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.0000027 ( 0 hom. )
Consequence
DCLK1
NM_001330071.2 missense
NM_001330071.2 missense
Scores
5
9
5
Clinical Significance
Conservation
PhyloP100: 9.19
Publications
0 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]
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ACMG classification
Classification was made for transcript
Our verdict: Uncertain_significance. The variant received 0 ACMG points.
Transcripts
RefSeq
Ensembl
Frequencies
GnomAD3 genomes 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 32 show subpopulations
GnomAD3 genomes
AF:
AC:
3
AN:
152242
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD4 exome AF: 0.00000274 AC: 4AN: 1461462Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2AN XY: 727058 show subpopulations
GnomAD4 exome
AF:
AC:
4
AN:
1461462
Hom.:
Cov.:
30
AF XY:
AC XY:
2
AN XY:
727058
show subpopulations
African (AFR)
AF:
AC:
0
AN:
33470
American (AMR)
AF:
AC:
0
AN:
44616
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
26120
East Asian (EAS)
AF:
AC:
1
AN:
39660
South Asian (SAS)
AF:
AC:
0
AN:
86204
European-Finnish (FIN)
AF:
AC:
0
AN:
53398
Middle Eastern (MID)
AF:
AC:
0
AN:
5768
European-Non Finnish (NFE)
AF:
AC:
0
AN:
1111850
Other (OTH)
AF:
AC:
3
AN:
60376
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.538
Heterozygous variant carriers
0
1
1
2
2
3
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
GnomAD4 genome 0.0000197 AC: 3AN: 152242Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74382 show subpopulations
GnomAD4 genome
AF:
AC:
3
AN:
152242
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74382
show subpopulations
African (AFR)
AF:
AC:
0
AN:
41470
American (AMR)
AF:
AC:
0
AN:
15280
Ashkenazi Jewish (ASJ)
AF:
AC:
0
AN:
3472
East Asian (EAS)
AF:
AC:
2
AN:
5202
South Asian (SAS)
AF:
AC:
0
AN:
4836
European-Finnish (FIN)
AF:
AC:
0
AN:
10624
Middle Eastern (MID)
AF:
AC:
0
AN:
316
European-Non Finnish (NFE)
AF:
AC:
0
AN:
68038
Other (OTH)
AF:
AC:
1
AN:
2092
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.492
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Feb 17, 2024
Ambry Genetics
Significance:Uncertain significance
Review Status:criteria provided, single submitter
Collection Method:clinical testing
The c.1880T>C (p.M627T) alteration is located in exon 15 (coding exon 14) of the DCLK1 gene. This alteration results from a T to C substitution at nucleotide position 1880, causing the methionine (M) at amino acid position 627 to be replaced by a threonine (T). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Pathogenic
BayesDel_addAF
Pathogenic
D
BayesDel_noAF
Uncertain
DANN
Uncertain
DEOGEN2
Benign
.;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
D
MetaRNN
Uncertain
D;D;D;D
MetaSVM
Benign
T
MutationAssessor
Benign
.;L;.;L
PhyloP100
PrimateAI
Pathogenic
D
PROVEAN
Pathogenic
.;D;D;D
REVEL
Uncertain
Sift
Uncertain
.;D;D;D
Sift4G
Uncertain
D;D;D;T
Polyphen
B;P;B;P
Vest4
MutPred
0.66
.;Gain of catalytic residue at L629 (P = 0.0195);.;Gain of catalytic residue at L629 (P = 0.0195);
MVP
MPC
2.2
ClinPred
D
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at
Publications
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