rs4859537

Positions:

• chr4-75601477-A-G
• chr4-75601477-A-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330724.2(CDKL2):​c.796-1108T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.87 in 152,050 control chromosomes in the GnomAD database, including 57,575 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.87 (57575 hom., cov: 32)
• Consequence: CDKL2 NM_001330724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.100

Genes affected

CDKL2 (HGNC:1782): (cyclin dependent kinase like 2) This gene product is a member of a large family of CDC2-related serine/threonine protein kinases. It accumulates primarily in the cytoplasm, with lower levels in the nucleus. [provided by RefSeq, Jul 2008]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.99).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.898 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
CDKL2	NM_001330724.2	c.796-1108T>C		intron_variant		ENST00000307465.9	NP_001317653.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
CDKL2	ENST00000307465.9	c.796-1108T>C		intron_variant		2	NM_001330724.2	ENSP00000306340	P1
CDKL2	ENST00000429927.6	c.796-1108T>C		intron_variant		1		ENSP00000412365
CDKL2	ENST00000506234.1	c.*132-1108T>C		intron_variant, NMD_transcript_variant		2		ENSP00000422666

Frequencies

GnomAD3 genomes AF: 0.870 AC: 132171 AN: 151932 Hom.: 57521 Cov.: 32

Gnomad AFR AF: 0.865

Gnomad AMI AF: 0.911

Gnomad AMR AF: 0.879

Gnomad ASJ AF: 0.883

Gnomad EAS AF: 0.920

Gnomad SAS AF: 0.884

Gnomad FIN AF: 0.869

Gnomad MID AF: 0.875

Gnomad NFE AF: 0.865

Gnomad OTH AF: 0.860

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.870 AC: 132283 AN: 152050 Hom.: 57575 Cov.: 32 AF XY: 0.870 AC XY: 64680 AN XY: 74328

Gnomad4 AFR AF: 0.865

Gnomad4 AMR AF: 0.879

Gnomad4 ASJ AF: 0.883

Gnomad4 EAS AF: 0.920

Gnomad4 SAS AF: 0.884

Gnomad4 FIN AF: 0.869

Gnomad4 NFE AF: 0.865

Gnomad4 OTH AF: 0.860

Alfa AF: 0.867 Hom.: 18153

Bravo AF: 0.869

Asia WGS AF: 0.904 AC: 3096 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.50

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

LitVar

Other links and lift over

dbSNP: rs4859537; hg19: chr4-76526661;