rs267608554

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP6_ModerateBS2

The NM_001323289.2(CDKL5):​c.978-49_978-41delGTGTCAGCT variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000061 in 1,180,915 control chromosomes in the GnomAD database, with no homozygous occurrence. There are 15 hemizygotes in GnomAD. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.000018 ( 0 hom., 1 hem., cov: 22)
Exomes 𝑓: 0.000065 ( 0 hom. 14 hem. )

Consequence

CDKL5
NM_001323289.2 intron

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:2O:1

Conservation

PhyloP100: 1.61
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP6
Variant X-18603851-GTGTGTCAGC-G is Benign according to our data. Variant chrX-18603851-GTGTGTCAGC-G is described in ClinVar as [Likely_benign]. Clinvar id is 189544.Status of the report is criteria_provided_single_submitter, 1 stars.
BS2
High Hemizygotes in GnomAdExome4 at 14 XL gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
CDKL5NM_001323289.2 linkuse as main transcriptc.978-49_978-41delGTGTCAGCT intron_variant ENST00000623535.2 NP_001310218.1 O76039-2
CDKL5NM_001037343.2 linkuse as main transcriptc.978-49_978-41delGTGTCAGCT intron_variant NP_001032420.1 O76039-1
CDKL5NM_003159.3 linkuse as main transcriptc.978-49_978-41delGTGTCAGCT intron_variant NP_003150.1 O76039-1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
CDKL5ENST00000623535.2 linkuse as main transcriptc.978-49_978-41delGTGTCAGCT intron_variant 1 NM_001323289.2 ENSP00000485244.1 O76039-2

Frequencies

GnomAD3 genomes
AF:
0.0000179
AC:
2
AN:
111916
Hom.:
0
Cov.:
22
AF XY:
0.0000293
AC XY:
1
AN XY:
34108
show subpopulations
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000376
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000276
AC:
5
AN:
180942
Hom.:
0
AF XY:
0.00
AC XY:
0
AN XY:
66832
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000622
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000655
AC:
70
AN:
1068999
Hom.:
0
AF XY:
0.0000414
AC XY:
14
AN XY:
338301
show subpopulations
Gnomad4 AFR exome
AF:
0.000116
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000809
Gnomad4 OTH exome
AF:
0.0000222
GnomAD4 genome
AF:
0.0000179
AC:
2
AN:
111916
Hom.:
0
Cov.:
22
AF XY:
0.0000293
AC XY:
1
AN XY:
34108
show subpopulations
Gnomad4 AFR
AF:
0.00
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000376
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000214
Hom.:
1
Bravo
AF:
0.0000340

ClinVar

Significance: Likely benign
Submissions summary: Benign:2Other:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Benign:1
Likely benign, no assertion criteria providedcurationRettBASEMar 13, 2014Unlikely to be pathogenic, not predicted to change splicing; however, there is no empirical evidence for this -
CDKL5 disorder Benign:1
Likely benign, criteria provided, single submittercurationCentre for Population Genomics, CPGSep 09, 2024This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as likely benign. At least the following criteria are met: Synonymous or intronic variant outside donor and acceptor splice regions where splicing prediction algorithms do not support significant splicing alteration (spliceAI score <=0.1) (BP4, BP7). -
not provided Other:1
not provided, flagged submissionliterature onlyRettBASE-- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs267608554; hg19: chrX-18621971; API