NM_001323289.2(CDKL5):c.549_552del (p.Leu184fs) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Apr 7, 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:: RCV002515944.3

Allele description [Variation Report for NM_001323289.2(CDKL5):c.549_552del (p.Leu184fs)]

NM_001323289.2(CDKL5):c.549_552del (p.Leu184fs)

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.549_552del (p.Leu184fs)

HGVS:

NC_000023.11:g.18584348_18584351del
NG_008475.1:g.163744_163747del
NM_001037343.2:c.549_552del
NM_001323289.2:c.549_552delMANE SELECT
NM_003159.3:c.549_552del
NP_001032420.1:p.Leu184fs
NP_001310218.1:p.Leu184fs
NP_003150.1:p.Leu184fs
NC_000023.10:g.18602465_18602468del
NC_000023.10:g.18602468_18602471del
NM_003159.2:c.549_552delACTT
p.L184Afsx43

Protein change:

L184fs

Links:

dbSNP: rs587783111

NCBI 1000 Genomes Browser:

rs587783111

Molecular consequence:

NM_001037343.2:c.549_552del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001323289.2:c.549_552del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_003159.3:c.549_552del - 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
SCV003461837	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Apr 7, 2022)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 29655203, 22872100, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003461837

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Apr 7, 2022)

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

Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.

Lindy AS, Stosser MB, Butler E, Downtain-Pickersgill C, Shanmugham A, Retterer K, Brandt T, Richard G, McKnight DA.

Epilepsia. 2018 May;59(5):1062-1071. doi: 10.1111/epi.14074. Epub 2018 Apr 14.

PubMed [citation]

PMID:: 29655203

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV003461837.2

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

Description

This premature translational stop signal has been observed in individual(s) with clinical features of CDKL5-related conditions (PMID: 29655203). This sequence change creates a premature translational stop signal (p.Leu184Alafs*43) 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). This variant is not present in population databases (gnomAD no frequency). ClinVar contains an entry for this variant (Variation ID: 156639). 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: Sep 29, 2024

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