rs1295816474

Variant names:

• chr14-50395843-T-C
• NM_004196.7:c.26A>G

Your query was ambiguous. Multiple possible variants found:

• chr14-50395843-T-C
• chr14-50395843-T-G

Variant summary

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

The NM_004196.7(CDKL1):​c.26A>G​(p.Lys9Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,459,680 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/19 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: 0.0000014 (0 hom.)
• Consequence: CDKL1 NM_004196.7 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.26

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

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=0.15757805).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKL1	NM_004196.7	c.26A>G	p.Lys9Arg	missense_variant	Exon 2 of 10	ENST00000395834.6	NP_004187.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
CDKL1	ENST00000395834.6	c.26A>G	p.Lys9Arg	missense_variant	Exon 2 of 10	1	NM_004196.7	ENSP00000379176.2
CDKL1	ENST00000216378.2	c.29A>G	p.Lys10Arg	missense_variant	Exon 2 of 9	1		ENSP00000216378.2
CDKL1	ENST00000356146.5	n.596A>G		non_coding_transcript_exon_variant	Exon 5 of 20	1
CDKL1	ENST00000531052.1	n.234A>G		non_coding_transcript_exon_variant	Exon 1 of 3	3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1459680 Hom.: 0 Cov.: 28 AF XY: 0.00 AC XY: 0 AN XY: 726326

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000180

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.095
BayesDel_addAF	Benign	-0.025	T
BayesDel_noAF	Benign	-0.27
CADD	Benign	23
DANN	Uncertain	0.99
Eigen	Benign	0.013
Eigen_PC	Benign	0.097
FATHMM_MKL	Uncertain	0.93	D
M_CAP	Benign	0.031	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.62	T
PrimateAI	Uncertain	0.69	T
PROVEAN	Benign	-1.6	N;N
REVEL	Benign	0.25
Sift	Benign	0.49	T;T
Sift4G	Benign	0.26	T;T
Vest4		0.17
MVP		0.18
MPC		0.22
ClinPred		0.67	D
GERP RS		4.3
gMVP		0.34

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: chr14-50862561;