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NM_001323289.2(CDKL5):c.872G>A (p.Cys291Tyr) AND multiple conditions

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Aug 15, 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:
RCV001203327.7

Allele description [Variation Report for NM_001323289.2(CDKL5):c.872G>A (p.Cys291Tyr)]

NM_001323289.2(CDKL5):c.872G>A (p.Cys291Tyr)

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.872G>A (p.Cys291Tyr)
Other names:
NM_001323289.2(CDKL5):c.872G>A
HGVS:
  • NC_000023.11:g.18598508G>A
  • NG_008475.1:g.177904G>A
  • NM_001037343.2:c.872G>A
  • NM_001323289.2:c.872G>AMANE SELECT
  • NM_003159.3:c.872G>A
  • NP_001032420.1:p.Cys291Tyr
  • NP_001310218.1:p.Cys291Tyr
  • NP_003150.1:p.Cys291Tyr
  • NP_003150.1:p.Cys291Tyr
  • NC_000023.10:g.18616628G>A
  • NM_003159.2:c.872G>A
  • O76039:p.Cys291Tyr
Protein change:
C291Y; CYS291TYR
Links:
RettBASE (CDKL5): 62; UniProtKB: O76039#VAR_058029; OMIM: 300203.0012; dbSNP: rs267606714
NCBI 1000 Genomes Browser:
rs267606714
Molecular consequence:
  • NM_001037343.2:c.872G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323289.2:c.872G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003159.3:c.872G>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
SCV001374486Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))
Uncertain significance
(Aug 15, 2022)
germlineclinical testing

PubMed (3)
[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

CDKL5 mutations in boys with severe encephalopathy and early-onset intractable epilepsy.

Elia M, Falco M, Ferri R, Spalletta A, Bottitta M, Calabrese G, Carotenuto M, Musumeci SA, Lo Giudice M, Fichera M.

Neurology. 2008 Sep 23;71(13):997-9. doi: 10.1212/01.wnl.0000326592.37105.88.

PubMed [citation]
PMID:
18809835

There is variability in the attainment of developmental milestones in the CDKL5 disorder.

Fehr S, Leonard H, Ho G, Williams S, de Klerk N, Forbes D, Christodoulou J, Downs J.

J Neurodev Disord. 2015;7(1):2. doi: 10.1186/1866-1955-7-2. Epub 2015 Jan 5.

PubMed [citation]
PMID:
25657822
PMCID:
PMC4318547
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001374486.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. 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: 11505). This missense change has been observed in individual(s) with clinical features of CDKL5-related disorder (PMID: 18809835, 25657822). This variant is not present in population databases (gnomAD no frequency). This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 291 of the CDKL5 protein (p.Cys291Tyr).

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

Last Updated: Feb 28, 2024