Evidence Repository
The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]
  • Gene obtained from curated document aligns with the Allele Registry but not with ClinVar data
  • No CSPEC computed assertion could be determined for this classification!

Variant: NM_001323289.2(CDKL5):c.2500C>T (p.Gln834Ter)

CA121519

11500 (ClinVar)

Gene: CDKL5
Condition: CDKL5 disorder
Inheritance Mode: X-linked inheritance
Link to MONDO
UUID: 88fe8ef5-c6a1-44f0-8176-fce1e98c77c7
Approved on: 2024-10-30
Published on: 2024-12-04

HGVS expressions

NM_001323289.2:c.2500C>T
NM_001323289.2(CDKL5):c.2500C>T (p.Gln834Ter)
NC_000023.11:g.18628374C>T
CM000685.2:g.18628374C>T
NC_000023.10:g.18646494C>T
CM000685.1:g.18646494C>T
NC_000023.9:g.18556415C>T
NG_008475.1:g.207770C>T
ENST00000623535.2:c.2500C>T
ENST00000674046.1:c.2623C>T
ENST00000379989.6:c.2500C>T
ENST00000379996.7:c.2500C>T
ENST00000623535.1:c.2500C>T
NM_001037343.1:c.2500C>T
NM_003159.2:c.2500C>T
NM_001323289.1:c.2500C>T
NM_001037343.2:c.2500C>T
NM_003159.3:c.2500C>T
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Pathogenic

Met criteria codes 4
PP4 PM6 PVS1 PM2_Supporting

Evidence Links 0

Expert Panel

Criteria Specification Information

Criteria Specification: ClinGen Rett and Angelman-like Disorders Expert Panel Specifications to the ACMG/AMP Variant Interpretation Guidelines for CDKL5 Version 3.0.0

Criteria Specification Approval History
Criteria Specifications for this VCEP
Evidence submitted by expert panel
Rett and Angelman-like Disorders VCEP
The p.Gln834Ter variant in CDKL5 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The p.Gln834Ter variant in CDKL5 is absent from gnomAD v4.1 (PM2_Supporting). The p.Gln834Ter variant in CDKL5 has been reported in an individual with a clinical phenotype suggestive of CDKL5 disorder (PMID: 16813600) (PP4). The p.Gln834Ter variant in CDKL5 occurs in the de novo state (biological parentage unconfirmed) in this individual (PM6). In summary, the p.Gln834Ter variant in CDKL5 is classified as Pathogenic for CDKL5 disorder based on the ACMG/AMP criteria (PVS1, PM2_Supporting, PP4, PM6).
Met criteria codes
PP4
The p.Gln834Ter variant in CDKL5 has been reported in an individual with a clinical phenotype suggestive of CDKL5 disorder (PMID: 16813600).
PM6
PM6: The p.Gln834Ter variant in CDKL5 occurs in the de novo state (biological parentage unconfirmed) in this individual.
PVS1
PVS1 is applicable, variant is upstream of p.R948. The p.Gln834Ter variant in CDKL5 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene where loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic.
PM2_Supporting
The p.Gln834Ter variant in CDKL5 is absent from gnomAD v4.1 (PM2_Supporting).
Curation History
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