GeneBe

rs745969938

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001323289.2(CDKL5):​c.145+15_145+28delATATATATATATAT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000195 in 513,039 control chromosomes in the GnomAD database, with no homozygous occurrence. There are no hemizygote samples in GnomAD. It is difficult to determine the true allele frequency of this variant because it is of type DEL_BIG, and the frequency of such variant types in population databases may be underestimated and unreliable. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 19)
Exomes 𝑓: 0.0000019 ( 0 hom. 0 hem. )

Consequence

CDKL5
NM_001323289.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 1.26

Publications

0 publications found
Variant links:
Genes affected
CDKL5 (HGNC:11411): (cyclin dependent kinase like 5) This gene is a member of Ser/Thr protein kinase family and encodes a phosphorylated protein with protein kinase activity. Mutations in this gene have been associated with X-linked infantile spasm syndrome (ISSX), also known as X-linked West syndrome, and Rett syndrome (RTT). Alternate transcriptional splice variants have been characterized. [provided by RefSeq, Jul 2008]
CDKL5 Gene-Disease associations (from GenCC):
  • CDKL5 disorder
    Inheritance: XL Classification: DEFINITIVE Submitted by: ClinGen
  • developmental and epileptic encephalopathy, 2
    Inheritance: XL Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: Orphanet, G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
  • atypical Rett syndrome
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • genetic developmental and epileptic encephalopathy
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • infantile spasms
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • precocious puberty
    Inheritance: XL Classification: LIMITED Submitted by: Ambry Genetics

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
CDKL5NM_001323289.2 linkc.145+15_145+28delATATATATATATAT intron_variant Intron 4 of 17 ENST00000623535.2 NP_001310218.1 O76039-2
CDKL5NM_001037343.2 linkc.145+15_145+28delATATATATATATAT intron_variant Intron 5 of 21 NP_001032420.1 O76039-1
CDKL5NM_003159.3 linkc.145+15_145+28delATATATATATATAT intron_variant Intron 4 of 20 NP_003150.1 O76039-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
CDKL5ENST00000623535.2 linkc.145+5_145+18delATATATATATATAT splice_region_variant, intron_variant Intron 4 of 17 1 NM_001323289.2 ENSP00000485244.1 O76039-2

Frequencies

GnomAD3 genomes
Cov.:
19
GnomAD4 exome
AF:
0.00000195
AC:
1
AN:
513039
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
125429
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.00
AC:
0
AN:
13389
American (AMR)
AF:
0.00
AC:
0
AN:
24992
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
12214
East Asian (EAS)
AF:
0.00
AC:
0
AN:
19269
South Asian (SAS)
AF:
0.00
AC:
0
AN:
29143
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
28779
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
2004
European-Non Finnish (NFE)
AF:
0.00000278
AC:
1
AN:
359626
Other (OTH)
AF:
0.00
AC:
0
AN:
23623
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.225
Heterozygous variant carriers
0
0
1
1
2
2
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<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
Cov.:
19

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
1.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs745969938; hg19: chrX-18582646; API