U.S. flag

An official website of the United States government

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

Germline classification:
Likely pathogenic (1 submission)
Last evaluated:
Apr 14, 2023
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
Somatic classification
of clinical impact:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Somatic classification
of oncogenicity:
None
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
Record status:
current
Accession:
RCV003235440.2

Allele description [Variation Report for NM_001323289.2(CDKL5):c.65G>A (p.Gly22Glu)]

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

Gene:
CDKL5:cyclin dependent kinase like 5 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Xp22.13
Genomic location:
Preferred name:
NM_001323289.2(CDKL5):c.65G>A (p.Gly22Glu)
Other names:
NM_001323289.2(CDKL5):c.65G>A; p.Gly22Glu
HGVS:
  • NC_000023.11:g.18510820G>A
  • NG_008475.1:g.90216G>A
  • NM_001037343.2:c.65G>A
  • NM_001323289.2:c.65G>AMANE SELECT
  • NM_003159.3:c.65G>A
  • NP_001032420.1:p.Gly22Glu
  • NP_001310218.1:p.Gly22Glu
  • NP_003150.1:p.Gly22Glu
  • NC_000023.10:g.18528940G>A
Protein change:
G22E
Links:
dbSNP: rs1602232972
NCBI 1000 Genomes Browser:
rs1602232972
Molecular consequence:
  • NM_001037343.2:c.65G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323289.2:c.65G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003159.3:c.65G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
CDKL5 disorder
Identifiers:
MONDO: MONDO:0100039; MedGen: CN296942

Recent activity

Clear Turn Off Turn On

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

See more...

Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003933679ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel
reviewed by expert panel

(ClinGen RettAS ACMG Specifications V2)		Likely pathogenic
(Apr 14, 2023) 		germlinecuration

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Details of each submission

From ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel, SCV003933679.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

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).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: May 16, 2025