rs4859537

Variant names:

• chr4-75601477-A-G
• rs4859537
• NM_001330724.2:c.796-1108T>C

Your query was ambiguous. Multiple possible variants found:

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

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 3 publications found

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

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001330724.2. 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
	CDKL2	NM_001330724.2	MANE Select	c.796-1108T>C		intron	N/A	NP_001317653.1	J3KNE8
	CDKL2	NM_003948.5		c.796-1108T>C		intron	N/A	NP_003939.1	Q92772

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL2	ENST00000307465.9	TSL:2 MANE Select	c.796-1108T>C		intron	N/A	ENSP00000306340.4	J3KNE8
	CDKL2	ENST00000429927.6	TSL:1	c.796-1108T>C		intron	N/A	ENSP00000412365.2	Q92772
	CDKL2	ENST00000943253.1		c.796-1108T>C		intron	N/A	ENSP00000613312.1

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

African (AFR) AF: 0.865 AC: 35911 AN: 41496

American (AMR) AF: 0.879 AC: 13420 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.883 AC: 3065 AN: 3470

East Asian (EAS) AF: 0.920 AC: 4767 AN: 5180

South Asian (SAS) AF: 0.884 AC: 4261 AN: 4820

European-Finnish (FIN) AF: 0.869 AC: 9167 AN: 10548

Middle Eastern (MID) AF: 0.872 AC: 253 AN: 290

European-Non Finnish (NFE) AF: 0.865 AC: 58798 AN: 67954

Other (OTH) AF: 0.860 AC: 1814 AN: 2110

Alfa AF: 0.867 Hom.: 21053

Bravo AF: 0.869

Asia WGS AF: 0.904 AC: 3096 AN: 3426

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.99
CADD	Benign	1.6
DANN	Benign	0.50
PhyloP100		-0.10
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs4859537; hg19: chr4-76526661;