chr13-35793401-G-T

Variant names:

• chr13-35793401-G-T
• NM_001330071.2:c.2023C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001330071.2(DCLK1):​c.2023C>A​(p.Pro675Thr) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,004 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict 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: 6.9e-7 (0 hom.)
• Consequence: DCLK1 NM_001330071.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.33

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 Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13824162).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
DCLK1	NM_001330071.2	c.2023C>A	p.Pro675Thr	missense_variant	Exon 16 of 17	ENST00000360631.8	NP_001317000.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
DCLK1	ENST00000360631.8	c.2023C>A	p.Pro675Thr	missense_variant	Exon 16 of 17	5	NM_001330071.2	ENSP00000353846.3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.86e-7 AC: 1 AN: 1457004 Hom.: 0 Cov.: 30 AF XY: 0.00000138 AC XY: 1 AN XY: 724726

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000254

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

Asia WGS AF: 0.000289 AC: 1 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.069
BayesDel_addAF	Benign	-0.059	T
BayesDel_noAF	Benign	-0.32
CADD	Benign	22
DANN	Benign	0.87
DEOGEN2	Benign	0.14	.;T;.;.
Eigen	Benign	-0.16
Eigen_PC	Benign	0.011
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Benign	0.85	T;D;D;D
M_CAP	Benign	0.0072	T
MetaRNN	Benign	0.14	T;T;T;T
MetaSVM	Benign	-0.83	T
MutationAssessor	Benign	1.3	.;L;.;L
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-0.51	.;N;N;N
REVEL	Benign	0.050
Sift	Benign	0.48	.;T;T;T
Sift4G	Benign	0.25	T;T;T;T
Polyphen		0.012	B;B;B;B
Vest4		0.41
MutPred		0.34		.;Gain of catalytic residue at K674 (P = 0);.;Gain of catalytic residue at K674 (P = 0);
MVP		0.51
MPC		1.3
ClinPred		0.71	D
GERP RS		4.6
Varity_R		0.20
gMVP		0.44

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr13-36367538;