rs267608478
Positions:
Variant summary
Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_StrongBP6BS1BS2
The NM_001323289.2(CDKL5):c.463+22T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000391 in 1,044,977 control chromosomes in the GnomAD database, including 1 homozygotes. There are 124 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).
Frequency
Genomes: 𝑓 0.00025 ( 0 hom., 7 hem., cov: 22)
Exomes 𝑓: 0.00041 ( 1 hom. 117 hem. )
Consequence
CDKL5
NM_001323289.2 intron
NM_001323289.2 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.128
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 Benign. Variant got -13 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.71).
BP6
?
Variant X-18581972-T-C is Benign according to our data. Variant chrX-18581972-T-C is described in ClinVar as [Benign]. Clinvar id is 156089.Status of the report is no_assertion_criteria_provided, 0 stars.
BS1
?
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000251 (28/111597) while in subpopulation NFE AF= 0.000491 (26/52995). AF 95% confidence interval is 0.000343. There are 0 homozygotes in gnomad4. There are 7 alleles in male gnomad4 subpopulation. Median coverage is 22. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 7 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.463+22T>C | intron_variant | ENST00000623535.2 | |||
CDKL5 | NM_001037343.2 | c.463+22T>C | intron_variant | ||||
CDKL5 | NM_003159.3 | c.463+22T>C | intron_variant |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.463+22T>C | intron_variant | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.000251 AC: 28AN: 111597Hom.: 0 Cov.: 22 AF XY: 0.000207 AC XY: 7AN XY: 33801
GnomAD3 genomes
?
AF:
AC:
28
AN:
111597
Hom.:
Cov.:
22
AF XY:
AC XY:
7
AN XY:
33801
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.000177 AC: 32AN: 180301Hom.: 0 AF XY: 0.000261 AC XY: 17AN XY: 65141
GnomAD3 exomes
AF:
AC:
32
AN:
180301
Hom.:
AF XY:
AC XY:
17
AN XY:
65141
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000408 AC: 381AN: 933380Hom.: 1 Cov.: 17 AF XY: 0.000464 AC XY: 117AN XY: 252226
GnomAD4 exome
AF:
AC:
381
AN:
933380
Hom.:
Cov.:
17
AF XY:
AC XY:
117
AN XY:
252226
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.000251 AC: 28AN: 111597Hom.: 0 Cov.: 22 AF XY: 0.000207 AC XY: 7AN XY: 33801
GnomAD4 genome
?
AF:
AC:
28
AN:
111597
Hom.:
Cov.:
22
AF XY:
AC XY:
7
AN XY:
33801
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:1Other:1
Revision: no assertion criteria provided
LINK: link
Submissions by phenotype
not specified Benign:1
Benign, no assertion criteria provided | curation | RettBASE | May 09, 2014 | Reported in multiple unaffected family members - |
not provided Other:1
not provided, flagged submission | literature only | RettBASE | - | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at