chr4-150199058-A-C

Variant names:

• chr4-150199058-A-C
• rs757132475
• ENST00000302176.8:c.992A>C

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001040261.5(DCLK2):​c.992A>C​(p.Tyr331Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Y331C) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 31)
• Consequence: DCLK2 NM_001040261.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.38
• 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.1662147).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040261.5. 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.961+955A>C		intron	N/A	NP_001035350.2	Q8N568-1
	DCLK2	NM_001040261.5		c.992A>C	p.Tyr331Ser	missense	Exon 5 of 17	NP_001035351.4	Q8N568-3
	DCLK2	NM_001410852.1		c.961+955A>C		intron	N/A	NP_001397781.1	Q8N568-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	DCLK2	ENST00000302176.8	TSL:1	c.992A>C	p.Tyr331Ser	missense	Exon 5 of 17	ENSP00000303887.8	Q8N568-3
	DCLK2	ENST00000296550.12	TSL:1 MANE Select	c.961+955A>C		intron	N/A	ENSP00000296550.7	Q8N568-1
	DCLK2	ENST00000411937.6	TSL:1	n.961+955A>C		intron	N/A	ENSP00000401916.2	G5E9L9

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 31

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.089	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	22
DANN	Benign	0.92
DEOGEN2	Benign	0.0055	T
Eigen	Benign	-0.25
Eigen_PC	Benign	-0.082
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Benign	0.77	T
M_CAP	Benign	0.013	T
MetaRNN	Benign	0.17	T
MetaSVM	Benign	-1.0	T
PhyloP100		4.4
PrimateAI	Benign	0.36	T
PROVEAN	Benign	0.16	N
REVEL	Benign	0.052
Sift	Benign	0.35	T
Sift4G	Benign	0.61	T
Polyphen		0.065	B
Vest4		0.39
MutPred		0.28		Loss of stability (P = 0.0295)
MVP		0.58
MPC		0.37
ClinPred		0.90	D
GERP RS		4.3
gMVP		0.37
Mutation Taster		=91/9	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.12		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: rs757132475; hg19: chr4-151120210;