rs267608666
Variant summary
Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_ModerateBP6_Moderate
The ENST00000379989.6(CDKL5):āc.2984T>Gā(p.Phe995Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/19 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. F995I) has been classified as Uncertain significance.
Frequency
Consequence
ENST00000379989.6 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -2 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
RS1 | NM_000330.4 | c.184+3218A>C | intron_variant | ENST00000379984.4 | |||
CDKL5 | NM_001037343.2 | c.2984T>G | p.Phe995Cys | missense_variant | 22/22 | ||
CDKL5 | NM_003159.3 | c.2984T>G | p.Phe995Cys | missense_variant | 21/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000379989.6 | c.2984T>G | p.Phe995Cys | missense_variant | 22/22 | 1 | |||
CDKL5 | ENST00000379996.7 | c.2984T>G | p.Phe995Cys | missense_variant | 21/21 | 1 | |||
RS1 | ENST00000379984.4 | c.184+3218A>C | intron_variant | 1 | NM_000330.4 | P1 | |||
CDKL5 | ENST00000673617.1 | n.256T>G | non_coding_transcript_exon_variant | 3/3 |
Frequencies
GnomAD3 genomes Cov.: 24
GnomAD3 exomes AF: 0.0000111 AC: 2AN: 180978Hom.: 0 AF XY: 0.0000305 AC XY: 2AN XY: 65598
GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00000547 AC: 6AN: 1097474Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 6AN XY: 362914
GnomAD4 genome Cov.: 24
ClinVar
Submissions by phenotype
not specified Benign:1
Likely benign, no assertion criteria provided | curation | RettBASE | Mar 13, 2014 | In exon 20, affecting only the transcript lowly expressed; In silico prediction: SIFT = tolerated, MutationTaster = polymorphism, PolyPhen2 = benign, AlignGVGD = benign (C0) - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 19, 2024 | This alteration is classified as likely benign based on a combination of the following: seen in unaffected individuals, population frequency, intact protein function, lack of segregation with disease, co-occurrence, RNA analysis, in silico models, amino acid conservation, lack of disease association in case-control studies, and/or the mechanism of disease or impacted region is inconsistent with a known cause of pathogenicity. - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at