NM_001323289.2(CDKL5):c.2343del (p.Arg781fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 15, 2018
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:: RCV000694825.6

Allele description [Variation Report for NM_001323289.2(CDKL5):c.2343del (p.Arg781fs)]

NM_001323289.2(CDKL5):c.2343del (p.Arg781fs)

Gene:

CDKL5:cyclin dependent kinase like 5 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

Xp22.13

Genomic location:

Preferred name:

NM_001323289.2(CDKL5):c.2343del (p.Arg781fs)

HGVS:

NC_000023.11:g.18619933del
NG_008475.1:g.199329del
NM_001037343.2:c.2343del
NM_001323289.2:c.2343delMANE SELECT
NM_003159.3:c.2343del
NP_001032420.1:p.Arg781fs
NP_001310218.1:p.Arg781fs
NP_003150.1:p.Arg781fs
NC_000023.10:g.18638052del
NC_000023.10:g.18638053del
NM_003159.2:c.2343delG

Protein change:

R781fs

Links:

RettBASE (CDKL5): 13; dbSNP: rs62643614

NCBI 1000 Genomes Browser:

rs62643614

Molecular consequence:

NM_001037343.2:c.2343del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001323289.2:c.2343del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003159.3:c.2343del - frameshift variant - [Sequence Ontology: SO:0001589]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000823287	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jan 15, 2018)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15917271, 22872100, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000823287

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jan 15, 2018)

germline

clinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

CDKL5 belongs to the same molecular pathway of MeCP2 and it is responsible for the early-onset seizure variant of Rett syndrome.

Mari F, Azimonti S, Bertani I, Bolognese F, Colombo E, Caselli R, Scala E, Longo I, Grosso S, Pescucci C, Ariani F, Hayek G, Balestri P, Bergo A, Badaracco G, Zappella M, Broccoli V, Renieri A, Kilstrup-Nielsen C, Landsberger N.

Hum Mol Genet. 2005 Jul 15;14(14):1935-46. Epub 2005 May 25.

PubMed [citation]

PMID:: 15917271

The CDKL5 disorder is an independent clinical entity associated with early-onset encephalopathy.

Fehr S, Wilson M, Downs J, Williams S, Murgia A, Sartori S, Vecchi M, Ho G, Polli R, Psoni S, Bao X, de Klerk N, Leonard H, Christodoulou J.

Eur J Hum Genet. 2013 Mar;21(3):266-73. doi: 10.1038/ejhg.2012.156. Epub 2012 Aug 8.

PubMed [citation]

PMID:: 22872100
PMCID:: PMC3573195

See all PubMed Citations (3)

Details of each submission

From Invitae, SCV000823287.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This variant has been reported to be de novo in an individual affected with an early onset seizure variant of Rett syndrome (PMID: 15917271). ClinVar contains an entry for this variant (Variation ID: 143801). This variant is not present in population databases (ExAC no frequency). This sequence change creates a premature translational stop signal (p.Arg781Serfs*3) in the CDKL5 gene. It is expected to result in an absent or disrupted protein product. Loss-of-function variants in CDKL5 are known to be pathogenic (PMID: 22872100). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Mar 5, 2024

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