NM_001330724.2:c.169-3116G>A

Variant names:

• chr4-75617565-C-T
• rs6852678
• NM_001330724.2:c.169-3116G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001330724.2(CDKL2):​c.169-3116G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.25 in 152,040 control chromosomes in the GnomAD database, including 5,043 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 0.25 (5043 hom., cov: 31)
• Consequence: CDKL2 NM_001330724.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0960
• Publications: 11 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=-0.95).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.289 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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL2	NM_001330724.2	MANE Select	c.169-3116G>A		intron	N/A	NP_001317653.1
	CDKL2	NM_003948.5		c.169-3116G>A		intron	N/A	NP_003939.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	CDKL2	ENST00000307465.9	TSL:2 MANE Select	c.169-3116G>A		intron	N/A	ENSP00000306340.4
	CDKL2	ENST00000429927.6	TSL:1	c.169-3116G>A		intron	N/A	ENSP00000412365.2
	CDKL2	ENST00000943253.1		c.169-3116G>A		intron	N/A	ENSP00000613312.1

Frequencies

GnomAD3 genomes AF: 0.250 AC: 38016 AN: 151922 Hom.: 5041 Cov.: 31

Gnomad AFR AF: 0.219

Gnomad AMI AF: 0.404

Gnomad AMR AF: 0.217

Gnomad ASJ AF: 0.338

Gnomad EAS AF: 0.0485

Gnomad SAS AF: 0.111

Gnomad FIN AF: 0.263

Gnomad MID AF: 0.366

Gnomad NFE AF: 0.292

Gnomad OTH AF: 0.275

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

GnomAD4 genome AF: 0.250 AC: 38034 AN: 152040 Hom.: 5043 Cov.: 31 AF XY: 0.245 AC XY: 18206 AN XY: 74314

African (AFR) AF: 0.219 AC: 9089 AN: 41480

American (AMR) AF: 0.216 AC: 3307 AN: 15284

Ashkenazi Jewish (ASJ) AF: 0.338 AC: 1171 AN: 3464

East Asian (EAS) AF: 0.0486 AC: 252 AN: 5184

South Asian (SAS) AF: 0.113 AC: 544 AN: 4818

European-Finnish (FIN) AF: 0.263 AC: 2774 AN: 10550

Middle Eastern (MID) AF: 0.360 AC: 105 AN: 292

European-Non Finnish (NFE) AF: 0.292 AC: 19850 AN: 67954

Other (OTH) AF: 0.273 AC: 574 AN: 2104

Alfa AF: 0.280 Hom.: 5341

Bravo AF: 0.246

Asia WGS AF: 0.110 AC: 383 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.95
CADD	Benign	7.3
DANN	Benign	0.36
PhyloP100		-0.096
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: rs6852678; hg19: chr4-76542749;