Variant: NM_001323289.2(CDKL5):c.65G>A (p.Gly22Glu)

CA412489767

803714 (ClinVar)

Gene: CDKL5

Condition: CDKL5 disorder

Inheritance Mode: X-linked inheritance

UUID: 9333188d-47cf-4c2d-abb7-5e45836da3d8

Approved on: 2023-04-14

Published on: 2023-06-16

HGVS expressions

NM_001323289.2:c.65G>A
NM_001323289.2(CDKL5):c.65G>A (p.Gly22Glu)
NC_000023.11:g.18510820G>A
CM000685.2:g.18510820G>A
NC_000023.10:g.18528940G>A
CM000685.1:g.18528940G>A
NC_000023.9:g.18438861G>A
NG_008475.1:g.90216G>A
ENST00000623535.2:c.65G>A
ENST00000635828.1:c.65G>A
ENST00000637881.1:c.65G>A
ENST00000674046.1:c.65G>A
ENST00000379989.6:c.65G>A
ENST00000379996.7:c.65G>A
ENST00000463994.4:c.65G>A
ENST00000623364.3:c.65G>A
ENST00000623535.1:n.65G>A
ENST00000624700.3:c.65G>A
NM_001037343.1:c.65G>A
NM_003159.2:c.65G>A
NM_001323289.1:c.65G>A
NM_001037343.2:c.65G>A
NM_003159.3:c.65G>A

Likely Pathogenic

• Met criteria codes: PM5 PM1 PM2_Supporting PP3

Expert Panel

Rett and Angelman-like Disorders VCEP

Criteria Specification Information

Evidence submitted by expert panel

Rett and Angelman-like Disorders VCEP

The p.Gly22Glu variant occurs in the well-characterized ATP binding region functional domain of the CDKL5 gene (PM1). A pathogenic missense variant (p.Gly22Ala) has been previously identified within this codon which indicates that this residue is critical to the function of the protein ( GeneDx internal database) (PM5). The p.Gly22Glu variant in CDKL5 is absent from gnomAD (PM2_supporting). Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own (PP3). In summary, the p.Gly22Glu variant in CDKL5 is classified as likely pathogenic for a CDKL5-related disorder based on the ACMG/AMP criteria (PM1, PM5, PM2_supporting, PP3).

Met criteria codes

• PM5: A pathogenic missense variant (p.Gly22Ala) has been previously identified within this codon which indicates that this residue is critical to the function of the protein ( GeneDx internal database)
• PM1: The p.Gly22Glu variant occurs in the well-characterized ATP binding region functional domain of the CDKL5 gene
• PM2_Supporting: The p.Gly22Glu variant in CDKL5 is absent from gnomAD
• PP3: Computational prediction analysis tools suggests a deleterious impact; however, this information does not predict clinical significance on its own