rs150900695
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The ENST00000379989.6(CDKL5):c.2994C>T(p.Phe998=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00043 in 1,209,395 control chromosomes in the GnomAD database, including 3 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 (★★).
Frequency
Genomes: 𝑓 0.0022 ( 1 hom., 65 hem., cov: 23)
Exomes 𝑓: 0.00025 ( 2 hom. 59 hem. )
Consequence
CDKL5
ENST00000379989.6 synonymous
ENST00000379989.6 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: 0.119
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]
RS1 (HGNC:10457): (retinoschisin 1) This gene encodes an extracellular protein that plays a crucial role in the cellular organization of the retina. The encoded protein is assembled and secreted from photoreceptors and bipolar cells as a homo-oligomeric protein complex. Mutations in this gene are responsible for X-linked retinoschisis, a common, early-onset macular degeneration in males that results in a splitting of the inner layers of the retina and severe loss in vision. [provided by RefSeq, Oct 2008]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.79).
BP6
?
Variant X-18653445-C-T is Benign according to our data. Variant chrX-18653445-C-T is described in ClinVar as [Benign]. Clinvar id is 136716.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
?
Synonymous conserved (PhyloP=0.119 with no splicing effect.
BS1
?
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00223 (249/111722) while in subpopulation AFR AF= 0.00738 (227/30742). AF 95% confidence interval is 0.0066. There are 1 homozygotes in gnomad4. There are 65 alleles in male gnomad4 subpopulation. Median coverage is 23. This position pass quality control queck.
BS2
?
High Hemizygotes in GnomAd4 at 65 XL gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RS1 | NM_000330.4 | c.184+3208G>A | intron_variant | ENST00000379984.4 | |||
CDKL5 | NM_001037343.2 | c.2994C>T | p.Phe998= | synonymous_variant | 22/22 | ||
CDKL5 | NM_003159.3 | c.2994C>T | p.Phe998= | synonymous_variant | 21/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000379989.6 | c.2994C>T | p.Phe998= | synonymous_variant | 22/22 | 1 | |||
CDKL5 | ENST00000379996.7 | c.2994C>T | p.Phe998= | synonymous_variant | 21/21 | 1 | |||
RS1 | ENST00000379984.4 | c.184+3208G>A | intron_variant | 1 | NM_000330.4 | P1 | |||
CDKL5 | ENST00000673617.1 | n.266C>T | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes ? AF: 0.00223 AC: 249AN: 111670Hom.: 1 Cov.: 23 AF XY: 0.00192 AC XY: 65AN XY: 33834
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GnomAD3 exomes AF: 0.000577 AC: 105AN: 181879Hom.: 0 AF XY: 0.000406 AC XY: 27AN XY: 66439
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GnomAD4 exome AF: 0.000247 AC: 271AN: 1097673Hom.: 2 Cov.: 31 AF XY: 0.000162 AC XY: 59AN XY: 363083
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GnomAD4 genome ? AF: 0.00223 AC: 249AN: 111722Hom.: 1 Cov.: 23 AF XY: 0.00192 AC XY: 65AN XY: 33896
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Oct 05, 2017 | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 30, 2013 | This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Athena Diagnostics | May 23, 2018 | - - |
History of neurodevelopmental disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 16, 2016 | General population or subpopulation frequency is too high to be a pathogenic mutation based on disease/syndrome prevalence and penetrance - |
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 24, 2024 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at