NM_001323289.2(CDKL5):c.872G>A (p.Cys291Tyr) AND Developmental and epileptic encephalopathy, 2

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Mar 13, 2014
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

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:: RCV000012260.27

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000032494	OMIM	no assertion criteria provided	Pathogenic (Sep 23, 2008)	germline	literature only	PubMed (1) [See all records that cite this PMID]
SCV000188404	RettBASE	no assertion criteria provided	Uncertain significance (Mar 13, 2014)	unknown	curation	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000032494

OMIM

no assertion criteria provided

Pathogenic
(Sep 23, 2008)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

SCV000188404

RettBASE

no assertion criteria provided

Uncertain significance
(Mar 13, 2014)

unknown

curation

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only
not provided	unknown	yes	1	not provided	not provided	1	not provided	curation

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

Details of each submission

From OMIM, SCV000032494.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 3-year-old Italian boy (patient 3) with developmental and epileptic encephalopathy (DEE2; 300672), Elia et al. (2008) identified a de novo hemizygous c.872G-A transition in the CDKL5 gene, resulting in a cys291-to-tyr (C291Y) substitution predicted to affect the catalytic domain of the protein. He had onset of seizures at age 2 months and mild dysmorphic features including high sloping forehead, hypotelorism, epicanthus, broad nasal bridge, high palate, and large anteverted ears. He later showed profound mental retardation and refractory epilepsy.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

From RettBASE, SCV000188404.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	not provided	not provided	curation	PubMed (1)

Description

"Not Rett syndrome - Severe encephalopathy and early-onset seizures"

PubMed [ID: 18809835]

Description

Conserved residue; In silico prediction: SIFT = deleterious, MutationTaster = disease-causing, PolyPhen2 = probably damaging, AlignGVGD = benign (C0)

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Feb 28, 2024

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