4-150079324-C-G

Variant names:

• chr4-150079324-C-G
• rs61744627
• NM_001040260.4:c.297C>G

Variant summary

Our verdict is Likely benign. The variant received -5 ACMG points: 0P and 5B. BP4 BS2

The NM_001040260.4(DCLK2):​c.297C>G​(p.Phe99Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000765 in 1,437,438 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000077 (0 hom.)
• Consequence: DCLK2 NM_001040260.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.669
• Publications: 1 publications found

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]

ACMG classification

Our verdict: Likely_benign. The variant received -5 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.2894399).
• BS2: High AC in GnomAdExome4 at 11 AD gene.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040260.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK2	NM_001040260.4	MANE Select	c.297C>G	p.Phe99Leu	missense	Exon 1 of 16	NP_001035350.2	Q8N568-1
	DCLK2	NM_001040261.5		c.297C>G	p.Phe99Leu	missense	Exon 1 of 17	NP_001035351.4	Q8N568-3
	DCLK2	NM_001410852.1		c.297C>G	p.Phe99Leu	missense	Exon 1 of 16	NP_001397781.1	Q8N568-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK2	ENST00000296550.12	TSL:1 MANE Select	c.297C>G	p.Phe99Leu	missense	Exon 1 of 16	ENSP00000296550.7	Q8N568-1
	DCLK2	ENST00000302176.8	TSL:1	c.297C>G	p.Phe99Leu	missense	Exon 1 of 17	ENSP00000303887.8	Q8N568-3
	DCLK2	ENST00000411937.6	TSL:1	n.297C>G		non_coding_transcript_exon	Exon 1 of 17	ENSP00000401916.2	G5E9L9

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000243 AC: 5 AN: 205464 AF XY: 0.0000271

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000765 AC: 11 AN: 1437438 Hom.: 0 Cov.: 31 AF XY: 0.0000140 AC XY: 10 AN XY: 712940

African (AFR) AF: 0.00 AC: 0 AN: 32782

American (AMR) AF: 0.00 AC: 0 AN: 41256

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25662

East Asian (EAS) AF: 0.00 AC: 0 AN: 38014

South Asian (SAS) AF: 0.000133 AC: 11 AN: 82692

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 51498

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1100264

Other (OTH) AF: 0.00 AC: 0 AN: 59518

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.0000165 AC: 2

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Pathogenic	0.74
BayesDel_addAF	Benign	-0.20	T
BayesDel_noAF	Benign	-0.25
CADD	Benign	19
DANN	Uncertain	0.99
DEOGEN2	Uncertain	0.69	D
Eigen	Benign	-0.27
Eigen_PC	Benign	-0.18
FATHMM_MKL	Benign	0.50	D
LIST_S2	Uncertain	0.94	D
M_CAP	Benign	0.035	D
MetaRNN	Benign	0.29	T
MetaSVM	Uncertain	0.14	D
MutationAssessor	Benign	1.3	L
PhyloP100		0.67
PrimateAI	Pathogenic	0.82	D
PROVEAN	Pathogenic	-4.9	D
REVEL	Uncertain	0.39
Sift	Benign	0.059	T
Sift4G	Benign	0.077	T
Polyphen		0.024	B
Vest4		0.11
MutPred		0.90		Gain of phosphorylation at S98 (P = 0.2465)
MVP		0.77
MPC		0.31
ClinPred		0.21	T
GERP RS		2.5
PromoterAI		0.028	Neutral
Varity_R		0.39
gMVP		0.66
Mutation Taster		=58/42	polymorphism

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

Other links and lift over

dbSNP: rs61744627; hg19: chr4-151000476;