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NM_001323289.2(CDKL5):c.455G>A (p.Cys152Tyr) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 20, 2022
Review status:
1 star out of maximum of 4 stars
criteria provided, single submitter
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:
RCV002530871.2

Allele description [Variation Report for NM_001323289.2(CDKL5):c.455G>A (p.Cys152Tyr)]

NM_001323289.2(CDKL5):c.455G>A (p.Cys152Tyr)

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.455G>A (p.Cys152Tyr)
HGVS:
  • NC_000023.11:g.18581942G>A
  • NG_008475.1:g.161338G>A
  • NM_001037343.2:c.455G>A
  • NM_001323289.2:c.455G>AMANE SELECT
  • NM_003159.3:c.455G>A
  • NP_001032420.1:p.Cys152Tyr
  • NP_001310218.1:p.Cys152Tyr
  • NP_003150.1:p.Cys152Tyr
  • NP_003150.1:p.Cys152Tyr
  • NC_000023.10:g.18600062G>A
  • NM_003159.2:c.455G>A
Protein change:
C152Y
Links:
dbSNP: rs122460157
NCBI 1000 Genomes Browser:
rs122460157
Molecular consequence:
  • NM_001037343.2:c.455G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323289.2:c.455G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003159.3:c.455G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
Developmental and epileptic encephalopathy, 2 (DEE2)
Synonyms:
INFANTILE SPASM SYNDROME, X-LINKED 2; Early infantile epileptic encephalopathy 2
Identifiers:
MONDO: MONDO:0010396; MedGen: C4750718; Orphanet: 1934; Orphanet: 3451; OMIM: 300672
Name:
Angelman syndrome-like
Identifiers:
MedGen: CN128785

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV002953859Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Pathogenic
(Sep 20, 2022)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Rare Variants in 48 Genes Account for 42% of Cases of Epilepsy With or Without Neurodevelopmental Delay in 246 Pediatric Patients.

Fernández-Marmiesse A, Roca I, Díaz-Flores F, Cantarín V, Pérez-Poyato MS, Fontalba A, Laranjeira F, Quintans S, Moldovan O, Felgueroso B, Rodríguez-Pedreira M, Simón R, Camacho A, Quijada P, Ibanez-Mico S, Domingno MR, Benito C, Calvo R, Pérez-Cejas A, Carrasco ML, Ramos F, Couce ML, et al.

Front Neurosci. 2019;13:1135. doi: 10.3389/fnins.2019.01135.

PubMed [citation]
PMID:
31780880
PMCID:
PMC6856296

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV002953859.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 152 of the CDKL5 protein (p.Cys152Tyr). This variant is not present in population databases (gnomAD no frequency). For these reasons, this variant has been classified as Pathogenic. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt CDKL5 protein function. ClinVar contains an entry for this variant (Variation ID: 495236). This missense change has been observed in individual(s) with clinical features of CDKL5-related conditions (PMID: 31780880). In at least one individual the variant was observed to be de novo.

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

Last Updated: Feb 28, 2024