14-50345027-A-T

Variant names:

• chr14-50345027-A-T
• NM_004196.7:c.322T>A

Variant summary

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

The NM_004196.7(CDKL1):​c.322T>A​(p.Trp108Arg) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 31)
• Consequence: CDKL1 NM_004196.7 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 6.81
• Publications: 0 publications found

Genes affected

CDKL1 (HGNC:1781): (cyclin dependent kinase like 1) This gene product is a member of a large family of CDC2-related serine/threonine protein kinases that accumulates primarily in the nucleus. [provided by RefSeq, Nov 2018]

ACMG classification

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004196.7. 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
	CDKL1	NM_004196.7	MANE Select	c.322T>A	p.Trp108Arg	missense	Exon 4 of 10	NP_004187.3
	CDKL1	NM_001423761.1		c.322T>A	p.Trp108Arg	missense	Exon 3 of 9	NP_001410690.1	Q00532-1
	CDKL1	NM_001423762.1		c.322T>A	p.Trp108Arg	missense	Exon 4 of 10	NP_001410691.1	A0A9S7JKS7

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL1	ENST00000395834.6	TSL:1 MANE Select	c.322T>A	p.Trp108Arg	missense	Exon 4 of 10	ENSP00000379176.2	A0A9S7JKS7
	CDKL1	ENST00000216378.2	TSL:1	c.325T>A	p.Trp109Arg	missense	Exon 4 of 9	ENSP00000216378.2	A0A5H1ZRP5
	CDKL1	ENST00000356146.5	TSL:1	n.2227-1969T>A		intron	N/A

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome Cov.: 30

GnomAD4 genome Cov.: 31

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	0.68
BayesDel_addAF	Uncertain	0.021	T
BayesDel_noAF	Benign	-0.21
CADD	Uncertain	25
DANN	Uncertain	0.98
Eigen	Benign	0.10
Eigen_PC	Uncertain	0.29
FATHMM_MKL	Uncertain	0.92	D
M_CAP	Benign	0.023	T
MetaRNN	Uncertain	0.60	D
MetaSVM	Benign	-1.0	T
PhyloP100		6.8
PROVEAN	Pathogenic	-11	D
REVEL	Uncertain	0.30
Sift	Benign	0.042	D
Sift4G	Uncertain	0.024	D
Vest4		0.71
MVP		0.14
MPC		0.46
ClinPred		0.98	D
GERP RS		5.5
gMVP		0.84
Mutation Taster		=11/89	disease causing

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.14		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

hg19: chr14-50811745;