rs786204954
Positions:
Variant summary
Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4BP6
The NM_001323289.2(CDKL5):c.2308C>A(p.Gln770Lys) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. Q770H) has been classified as Likely benign.
Frequency
Genomes: not found (cov: 23)
Exomes 𝑓: 0.0 ( 0 hom. 0 hem. )
Failed GnomAD Quality Control
Consequence
CDKL5
NM_001323289.2 missense
NM_001323289.2 missense
Scores
1
4
11
Clinical Significance
Conservation
PhyloP100: 4.42
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]
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ACMG classification
Classification made for transcript
Verdict is Uncertain_significance. Variant got 0 ACMG points.
PM2
?
Very rare variant in population databases, with high coverage;
BP4
?
Computational evidence support a benign effect (MetaRNN=0.28485432).
BP6
?
Variant X-18619898-C-A is Benign according to our data. Variant chrX-18619898-C-A is described in ClinVar as [Benign]. Clinvar id is 189532.Status of the report is no_assertion_criteria_provided, 0 stars.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.2308C>A | p.Gln770Lys | missense_variant | 16/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.2308C>A | p.Gln770Lys | missense_variant | 17/22 | ||
CDKL5 | NM_003159.3 | c.2308C>A | p.Gln770Lys | missense_variant | 16/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.2308C>A | p.Gln770Lys | missense_variant | 16/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? Cov.: 23
GnomAD3 genomes
?
Cov.:
23
GnomAD4 exome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0AN: 1084280Hom.: 0 Cov.: 26 AF XY: 0.00 AC XY: 0AN XY: 351372
GnomAD4 exome
Data not reliable, filtered out with message: AC0
AF:
AC:
0
AN:
1084280
Hom.:
Cov.:
26
AF XY:
AC XY:
0
AN XY:
351372
Gnomad4 AFR exome
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Gnomad4 AMR exome
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Gnomad4 EAS exome
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Gnomad4 SAS exome
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Gnomad4 FIN exome
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GnomAD4 genome ? Cov.: 23
GnomAD4 genome
?
Cov.:
23
ClinVar
Significance: Benign
Submissions summary: Benign: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 | Inherited from unaffected mother, both proband and mother with random XCI; In silico prediction: SIFT = tolerated, MutationTaster = polymorphism, PolyPhen2 = benign, AlignGVGD = benign (C0) - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T;T;T;.;.
FATHMM_MKL
Uncertain
D
M_CAP
Pathogenic
D
MetaRNN
Benign
T;T;T;T;T
MetaSVM
Benign
T
MutationAssessor
Benign
L;.;L;.;L
MutationTaster
Benign
N;N
PrimateAI
Uncertain
T
PROVEAN
Benign
N;.;N;.;.
REVEL
Benign
Sift
Uncertain
D;.;D;.;.
Sift4G
Benign
T;.;T;T;T
Polyphen
B;.;B;.;.
Vest4
MutPred
Gain of ubiquitination at Q770 (P = 0.0117);Gain of ubiquitination at Q770 (P = 0.0117);Gain of ubiquitination at Q770 (P = 0.0117);Gain of ubiquitination at Q770 (P = 0.0117);Gain of ubiquitination at Q770 (P = 0.0117);
MVP
MPC
0.46
ClinPred
D
GERP RS
Varity_R
gMVP
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