Genetic Variant CDKL1:n.2308C>T (chr14-50342977-G-A) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBS1BS2

The ENST00000356146.5(CDKL1):n.2308C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,356,348 control chromosomes in the GnomAD database, including 30 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 0.0069 ( 21 hom., cov: 32)

Exomes 𝑓: 0.00091 ( 9 hom. )

Consequence

CDKL1
ENST00000356146.5 non_coding_transcript_exon

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.40

Publications

1 publications found

Variant links:

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]

CDKL1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.81).

BS1

Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00693 (1054/152144) while in subpopulation AFR AF = 0.0242 (1005/41480). AF 95% confidence interval is 0.023. There are 21 homozygotes in GnomAd4. There are 500 alleles in the male GnomAd4 subpopulation. Median coverage is 32. This position passed quality control check.

BS2

High Homozygotes in GnomAd4 at 21 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
CDKL1	NM_004196.7 link	c.364-755C>T		intron_variant	Intron 4 of 9	ENST00000395834.6	NP_004187.3	Q00532

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
CDKL1	ENST00000356146.5 link	n.2308C>T	non_coding_transcript_exon_variant	Exon 16 of 20	1
CDKL1	ENST00000395834.6 link	c.364-755C>T	intron_variant	Intron 4 of 9	1	NM_004196.7	ENSP00000379176.2
CDKL1	ENST00000216378.2 link	c.367-755C>T	intron_variant	Intron 4 of 8	1		ENSP00000216378.2	Q00532-3A0A5H1ZRP5
CDKL1	ENST00000528197.5 link	n.422-755C>T	intron_variant	Intron 4 of 5	4

Frequencies

GnomAD3 genomes

AF:

0.00693

AC:

1053

AN:

152026

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0243

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00177

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000192

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000206

Gnomad OTH

AF:

0.00336

GnomAD2 exomes

AF:

0.00150

AC:

335

AN:

223716

AF XY:

0.00126

show subpopulations

Gnomad AFR exome

AF:

0.0225

Gnomad AMR exome

AF:

0.000646

Gnomad ASJ exome

AF:

0.000106

Gnomad EAS exome

AF:

0.000180

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000275

Gnomad OTH exome

AF:

0.000531

GnomAD4 exome

AF:

0.000908

AC:

1094

AN:

1204204

Hom.:

Cov.:

AF XY:

0.000792

AC XY:

472

AN XY:

595706

show subpopulations

African (AFR)

AF:

0.0255

AC:

662

AN:

25950

American (AMR)

AF:

0.000668

AC:

AN:

35936

Ashkenazi Jewish (ASJ)

AF:

0.0000603

AC:

AN:

16574

East Asian (EAS)

AF:

0.000123

AC:

AN:

16270

South Asian (SAS)

AF:

0.0000616

AC:

AN:

81210

European-Finnish (FIN)

AF:

0.00

AC:

AN:

30844

Middle Eastern (MID)

AF:

0.000224

AC:

AN:

4464

European-Non Finnish (NFE)

AF:

0.000354

AC:

336

AN:

949314

Other (OTH)

AF:

0.00144

AC:

AN:

43642

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

123

185

246

308

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.00693

AC:

1054

AN:

152144

Hom.:

Cov.:

AF XY:

0.00672

AC XY:

500

AN XY:

74364

show subpopulations

African (AFR)

AF:

0.0242

AC:

1005

AN:

41480

American (AMR)

AF:

0.00177

AC:

AN:

15272

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3464

East Asian (EAS)

AF:

0.000193

AC:

AN:

5190

South Asian (SAS)

AF:

0.00

AC:

AN:

4820

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10592

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000206

AC:

AN:

68014

Other (OTH)

AF:

0.00332

AC:

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.504

Heterozygous variant carriers

145

193

241

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

100

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00735

Hom.:

Bravo

AF:

0.00782

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.81

CADD

Benign

0.26

(source)

DANN

Benign

0.74

PhyloP100

-2.4

Mutation Taster

=100/0

polymorphism

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over