Evidence Repository - Clinical Genome Resources

The ClinGen Evidence Repository is an FDA-recognized human genetic variant database containing expert-curated assertions regarding variants' pathogenicity and supporting evidence summaries. [Disclaimer]

Variant: NM_003159.2(CDKL5):c.1247_1248delAG (p.Glu416Valfs)

CA235608

189554 (ClinVar)

Gene: CDKL5 (HGNC:6792)

Condition: CDKL5 disorder (MONDO:0100039)

Inheritance Mode: X-linked inheritance (dominant (HP:0001423))

UUID: 933d9c7c-3865-4a89-9a0a-565d7134d1a8

Approved on: 2021-03-26

Published on: 2021-05-17

HGVS expressions

NM_003159.2:c.1247_1248delAG

NM_003159.2:c.1247_1248del

NM_003159.2(CDKL5):c.1247_1248delAG (p.Glu416Valfs)

ENST00000623535.2:c.1247_1248del

ENST00000635828.1:c.1247_1248del

ENST00000637881.1:c.1247_1248del

ENST00000674046.1:c.1247_1248del

ENST00000379989.6:c.1247_1248del

ENST00000379996.7:c.1247_1248del

ENST00000463994.4:c.1247_1248del

ENST00000623535.1:n.1247_1248del

NM_001037343.1:c.1247_1248del

NM_001323289.1:c.1247_1248del

NM_001323289.2:c.1247_1248del

NM_001037343.2:c.1247_1248del

NM_003159.3:c.1247_1248del

NC_000023.11:g.18604171_18604172del

CM000685.2:g.18604171_18604172del

NC_000023.10:g.18622291_18622292del

CM000685.1:g.18622291_18622292del

NC_000023.9:g.18532212_18532213del

NG_008475.1:g.183567_183568del

Pathogenic

PVS1 PS4 PM2_Supporting PM6_Strong

Evidence Links 0

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Criteria Specifications for this VCEP

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Glu416Valfs variant in CDKL5 is predicted to cause a premature stop codon that leads to a truncated or absent protein in a gene in which loss-of-function is an established mechanism. There is significant evidence that loss of this region of the gene is pathogenic (PVS1). The p.Glu416Valfs variant has been observed in at least 5 individuals with CDKL5 disease (PMID: 27779742, 27864847, 23064044, ClinVar Variation ID 189554) (PS4). The p.XX variant in GENE has been reported in at least 2 de novo occurrences (biological parentage unconfirmed) in individuals with CDKL5 disorder (PMID XX) (PMID 27779742, 27864847) (PM6_strong). This variant is absent from gnomAD (PM2_supporting). In summary, this variant meets criteria to be classified as pathogenic for CDKL5-associated disorder based on the ACMG/AMP criteria applied (PVS1, PS4, PM6_strong, PM2_supporting).

PVS1

The p.(Glu416Valfs*2) 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.

PS4

The p.(Glu416Valfs*2) variant has been observed in at least 5 other individuals with CDKL5 disease (PMID: 27779742, PMID: 27864847, PMID: 23064044, ClinVar Variation ID 189554).

PM2_Supporting

The p.(Glu416Valfs*2) variant in CDKL5 is absent from gnomAD

PM6_Strong

The p.(Glu416Valfs*2) variant in CDKL5 has been reported in at least 2 unconfirmed de novo occurrences in individuals with early onset epileptic encephalopathy (PMID 27779742, PMID 27864847).

Curation History

The information on this website is not intended for direct diagnostic use or medical decision-making without review by a genetics professional. Individuals should not change their health behavior solely on the basis of information contained on this website. If you have questions about the information contained on this website, please see a health care professional.