chr4-150232793-A-G
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Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001040260.4(DCLK2):āc.1531A>Gā(p.Ile511Val) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.00031 in 1,614,126 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (ā ).
Frequency
Genomes: š 0.00022 ( 0 hom., cov: 33)
Exomes š: 0.00032 ( 0 hom. )
Consequence
DCLK2
NM_001040260.4 missense
NM_001040260.4 missense
Scores
2
8
9
Clinical Significance
Conservation
PhyloP100: 9.32
Genes affected
DCLK2 (HGNC:19002): (doublecortin like kinase 2) 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. Mouse studies show that the DCX gene, another family member, and this gene share function in the establishment of hippocampal organization and that their absence results in a severe epileptic phenotype and lethality, as described in human patients with lissencephaly. Multiple alternatively spliced transcript variants have been identified. [provided by RefSeq, Sep 2010]
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ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -6 ACMG points.
BP4
Computational evidence support a benign effect (MetaRNN=0.19918269).
BS2
High AC in GnomAd4 at 34 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
DCLK2 | NM_001040260.4 | c.1531A>G | p.Ile511Val | missense_variant | 10/16 | ENST00000296550.12 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
DCLK2 | ENST00000296550.12 | c.1531A>G | p.Ile511Val | missense_variant | 10/16 | 1 | NM_001040260.4 | P4 |
Frequencies
GnomAD3 genomes AF: 0.000230 AC: 35AN: 152188Hom.: 0 Cov.: 33
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GnomAD3 exomes AF: 0.000231 AC: 58AN: 251374Hom.: 0 AF XY: 0.000280 AC XY: 38AN XY: 135844
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GnomAD4 exome AF: 0.000319 AC: 466AN: 1461820Hom.: 0 Cov.: 31 AF XY: 0.000309 AC XY: 225AN XY: 727198
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GnomAD4 genome AF: 0.000223 AC: 34AN: 152306Hom.: 0 Cov.: 33 AF XY: 0.000161 AC XY: 12AN XY: 74474
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ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 19, 2022 | The c.1582A>G (p.I528V) alteration is located in exon 11 (coding exon 11) of the DCLK2 gene. This alteration results from a A to G substitution at nucleotide position 1582, causing the isoleucine (I) at amino acid position 528 to be replaced by a valine (V). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Uncertain
CADD
Uncertain
DANN
Uncertain
DEOGEN2
Benign
T;T;.;.
Eigen
Uncertain
Eigen_PC
Uncertain
FATHMM_MKL
Pathogenic
D
LIST_S2
Uncertain
D;D;D;D
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
N;.;.;.
MutationTaster
Benign
D;D;D
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;N
REVEL
Uncertain
Sift
Pathogenic
D;.;D;D
Sift4G
Uncertain
D;D;D;D
Polyphen
P;.;B;B
Vest4
MVP
MPC
0.93
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at