rs140332992
Variant summary
Our verdict is Likely benign. Variant got -5 ACMG points: 0P and 5B. BP7BS2
This summary comes from the ClinGen Evidence Repository: The p.Arg31= variant in CDKL5 is present in 3 female and 2 male individuals in gnomAD (0.002%) (not sufficient to meet BS1 criteria). The p.Arg31= variant is observed in at least 2 unaffected individuals (internal database) (BS2). The silent p.Arg31= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). In summary, the p.Arg31= variant in CDKL5 is classified as likely benign based on the ACMG/AMP criteria (BS2, BP7). LINK:https://erepo.genome.network/evrepo/ui/classification/CA171658/MONDO:0100039/016
Frequency
Consequence
NM_001323289.2 synonymous
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -5 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.93A>G | p.Arg31= | synonymous_variant | 3/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.93A>G | p.Arg31= | synonymous_variant | 4/22 | ||
CDKL5 | NM_003159.3 | c.93A>G | p.Arg31= | synonymous_variant | 3/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.93A>G | p.Arg31= | synonymous_variant | 3/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.0000448 AC: 5AN: 111724Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33898
GnomAD3 exomes AF: 0.0000219 AC: 4AN: 182437Hom.: 0 AF XY: 0.0000298 AC XY: 2AN XY: 67039
GnomAD4 exome AF: 0.0000237 AC: 25AN: 1057042Hom.: 0 Cov.: 24 AF XY: 0.0000274 AC XY: 9AN XY: 328494
GnomAD4 genome ? AF: 0.0000447 AC: 5AN: 111779Hom.: 0 Cov.: 23 AF XY: 0.00 AC XY: 0AN XY: 33963
ClinVar
Submissions by phenotype
not provided Uncertain:1Benign:2
Likely benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 19, 2020 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | May 01, 2022 | CDKL5: BP4, BP7 - |
Uncertain significance, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Mar 10, 2015 | - - |
not specified Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Aug 10, 2015 | - - |
CDKL5 disorder Benign:1
Likely benign, reviewed by expert panel | curation | ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel | Sep 01, 2022 | The p.Arg31= variant in CDKL5 is present in 3 female and 2 male individuals in gnomAD (0.002%) (not sufficient to meet BS1 criteria). The p.Arg31= variant is observed in at least 2 unaffected individuals (internal database) (BS2). The silent p.Arg31= variant is not predicted to affect splicing using multiple computational tools and does not affect a highly conserved nucleotide (BP7). In summary, the p.Arg31= variant in CDKL5 is classified as likely benign based on the ACMG/AMP criteria (BS2, BP7). - |
History of neurodevelopmental disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Jan 16, 2017 | In silico models in agreement (benign);Synonymous alterations with insufficient evidence to classify as benign - |
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at