NM_001323289.2(CDKL5):c.1648C>T (p.Arg550Ter) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jun 27, 2023
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:: RCV001244788.7

Allele description [Variation Report for NM_001323289.2(CDKL5):c.1648C>T (p.Arg550Ter)]

NM_001323289.2(CDKL5):c.1648C>T (p.Arg550Ter)

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.1648C>T (p.Arg550Ter)

Other names:

p.R550*:CGA>TGA; p.R550*; NM_001323289.2(CDKL5):c.1648C>T; p.Arg550Ter

HGVS:

NC_000023.11:g.18604572C>T
NG_008475.1:g.183968C>T
NM_001037343.2:c.1648C>T
NM_001323289.2:c.1648C>TMANE SELECT
NM_003159.3:c.1648C>T
NP_001032420.1:p.Arg550Ter
NP_001032420.1:p.Arg550Ter
NP_001310218.1:p.Arg550Ter
NP_003150.1:p.Arg550Ter
NP_003150.1:p.Arg550Ter
NC_000023.10:g.18622692C>T
NM_001037343.1:c.1648C>T
NM_001323289.1:c.1648C>T
NM_003159.2:c.1648C>T

Protein change:

R550*

Links:

RettBASE (CDKL5): 47; dbSNP: rs267608643

NCBI 1000 Genomes Browser:

rs267608643

Molecular consequence:

NM_001037343.2:c.1648C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001323289.2:c.1648C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_003159.3:c.1648C>T - nonsense - [Sequence Ontology: SO:0001587]

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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Homo sapiens leucine rich repeat protein 1 (LRR1), transcript variant 5, non-cod...
Homo sapiens leucine rich repeat protein 1 (LRR1), transcript variant 5, non-coding RNA
gi|1890351234|ref|NR_037793.2|

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001418032	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Jun 27, 2023)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18063413, 21318334, 22678952, 22872100, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001418032

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Jun 27, 2023)

germline

clinical testing

PubMed (5)
[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

Clinical and electroencephalographic features in patients with CDKL5 mutations: two new Italian cases and review of the literature.

Pintaudi M, Baglietto MG, Gaggero R, Parodi E, Pessagno A, Marchi M, Russo S, Veneselli E.

Epilepsy Behav. 2008 Feb;12(2):326-31. Epub 2007 Dec 11. Review.

PubMed [citation]

PMID:: 18063413

Identification of a novel CDKL5 exon and pathogenic mutations in patients with severe mental retardation, early-onset seizures and Rett-like features.

Rademacher N, Hambrock M, Fischer U, Moser B, Ceulemans B, Lieb W, Boor R, Stefanova I, Gillessen-Kaesbach G, Runge C, Korenke GC, Spranger S, Laccone F, Tzschach A, Kalscheuer VM.

Neurogenetics. 2011 May;12(2):165-7. doi: 10.1007/s10048-011-0277-6. Epub 2011 Feb 12. No abstract available.

PubMed [citation]

PMID:: 21318334

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV001418032.5

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

For these reasons, this variant has been classified as Pathogenic. ClinVar contains an entry for this variant (Variation ID: 143780). This premature translational stop signal has been observed in individuals with clinical features of CDKL5-related conditions (PMID: 18063413, 21318334, 22678952). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Arg550*) 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).

#	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: Oct 8, 2024

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