X-18625140-G-A
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2
The NM_001323289.2(CDKL5):c.2389G>A(p.Asp797Asn) variant causes a missense change. The variant allele was found at a frequency of 0.0000706 in 1,204,742 control chromosomes in the GnomAD database, including 1 homozygotes. There are 20 hemizygotes in GnomAD. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. D797H) has been classified as Likely benign.
Frequency
Consequence
NM_001323289.2 missense
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Benign. Variant got -20 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
CDKL5 | NM_001323289.2 | c.2389G>A | p.Asp797Asn | missense_variant | 17/18 | ENST00000623535.2 | |
CDKL5 | NM_001037343.2 | c.2389G>A | p.Asp797Asn | missense_variant | 18/22 | ||
CDKL5 | NM_003159.3 | c.2389G>A | p.Asp797Asn | missense_variant | 17/21 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
CDKL5 | ENST00000623535.2 | c.2389G>A | p.Asp797Asn | missense_variant | 17/18 | 1 | NM_001323289.2 | P1 |
Frequencies
GnomAD3 genomes AF: 0.0000457 AC: 5AN: 109344Hom.: 0 Cov.: 22 AF XY: 0.0000315 AC XY: 1AN XY: 31698
GnomAD3 exomes AF: 0.000279 AC: 51AN: 182916Hom.: 1 AF XY: 0.000148 AC XY: 10AN XY: 67428
GnomAD4 exome AF: 0.0000730 AC: 80AN: 1095349Hom.: 1 Cov.: 29 AF XY: 0.0000526 AC XY: 19AN XY: 360925
GnomAD4 genome AF: 0.0000457 AC: 5AN: 109393Hom.: 0 Cov.: 22 AF XY: 0.0000315 AC XY: 1AN XY: 31757
ClinVar
Submissions by phenotype
not specified Benign:2
Benign, no assertion criteria provided | curation | RettBASE | May 15, 2014 | Found in unaffected male and normal population, In silico prediction: SIFT = deleterious, MutationTaster = disease-causing, PolyPhen2 = possibly damaging, AlignGVGD = benign (C0) - |
Benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 19, 2024 | Variant summary: CDKL5 c.2389G>A (p.Asp797Asn) results in a conservative amino acid change in the encoded protein sequence. Four of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00028 in 182916 control chromosomes, predominantly at a frequency of 0.0015 within the Latino subpopulation in the gnomAD database, including 1 homozygote, and 5 hemizygotes, strongly suggesting that the variant is a benign polymorphism found primarily in populations of Latino origin. To our knowledge, no occurrence of c.2389G>A in individuals affected with Early Infantile Epileptic Encephalopathy 2 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 189533). Based on the evidence outlined above, the variant was classified as benign. - |
Developmental and epileptic encephalopathy, 2 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Mendelics | May 28, 2019 | - - |
Inborn genetic diseases Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Ambry Genetics | Dec 05, 2017 | 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. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Sep 09, 2020 | This variant is associated with the following publications: (PMID: 22867051) - |
Developmental and epileptic encephalopathy, 2;CN128785:Angelman syndrome-like Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 08, 2024 | - - |
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at