rs1677055215

Variant names:

• chr2-39204613-A-C
• rs1677055215
• NM_001397900.1:c.368T>G

Variant summary

Our verdict is Uncertain significance. The variant received 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_001397900.1(CDKL4):​c.368T>G​(p.Ile123Ser) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: CDKL4 NM_001397900.1 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 5.26
• Publications: 0 publications found

Genes affected

CDKL4 (HGNC:19287): (cyclin dependent kinase like 4) Predicted to enable cyclin-dependent protein serine/threonine kinase activity. Predicted to be involved in protein phosphorylation. Predicted to be located in cytoplasm. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Our verdict: Uncertain_significance. The variant received 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.929

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001397900.1. 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
	CDKL4	NM_001397900.1	MANE Select	c.368T>G	p.Ile123Ser	missense	Exon 5 of 10	NP_001384829.1	H7BZI6
	CDKL4	NM_001346911.1		c.368T>G	p.Ile123Ser	missense	Exon 4 of 9	NP_001333840.1	Q5MAI5-1
	CDKL4	NM_001009565.3		c.368T>G	p.Ile123Ser	missense	Exon 5 of 9	NP_001009565.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL4	ENST00000451199.7	TSL:2 MANE Select	c.368T>G	p.Ile123Ser	missense	Exon 5 of 10	ENSP00000389833.2	H7BZI6
	CDKL4	ENST00000395035.4	TSL:1	c.368T>G	p.Ile123Ser	missense	Exon 5 of 10	ENSP00000378476.3	Q5MAI5-1
	CDKL4	ENST00000378803.6	TSL:1	c.368T>G	p.Ile123Ser	missense	Exon 5 of 9	ENSP00000368080.1	Q5MAI5-2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 20

GnomAD4 genome Cov.: 32

Alfa AF: 0.0000745 Hom.: 0

Bravo AF: 0.00000756

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	0.57
BayesDel_addAF	Pathogenic	0.26	D
BayesDel_noAF	Uncertain	0.13
CADD	Uncertain	24
DANN	Uncertain	0.99
DEOGEN2	Benign	0.055	T
Eigen	Pathogenic	0.74
Eigen_PC	Pathogenic	0.72
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.97	D
M_CAP	Benign	0.062	D
MetaRNN	Pathogenic	0.93	D
MetaSVM	Uncertain	-0.060	T
MutationAssessor	Uncertain	2.5	M
PhyloP100		5.3
PrimateAI	Uncertain	0.64	T
PROVEAN	Pathogenic	-5.7	D
REVEL	Pathogenic	0.72
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.99	D
Vest4		0.77
MVP		0.89
MPC		0.59
ClinPred		1.0	D
GERP RS		5.6
Varity_R		0.96
gMVP		0.64
Mutation Taster		=88/12	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.47		Details are displayed if max score is > 0.2
DS_AL_spliceai		0.47		Position offset: 4

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1677055215; hg19: chr2-39431754;