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NM_001323289.2(CDKL5):c.2277G>A (p.Trp759Ter) AND multiple conditions

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Nov 23, 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:
RCV003802737.2

Allele description [Variation Report for NM_001323289.2(CDKL5):c.2277G>A (p.Trp759Ter)]

NM_001323289.2(CDKL5):c.2277G>A (p.Trp759Ter)

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.2277G>A (p.Trp759Ter)
HGVS:
  • NC_000023.11:g.18619867G>A
  • NG_008475.1:g.199263G>A
  • NM_001037343.2:c.2277G>A
  • NM_001323289.2:c.2277G>AMANE SELECT
  • NM_003159.3:c.2277G>A
  • NP_001032420.1:p.Trp759Ter
  • NP_001310218.1:p.Trp759Ter
  • NP_003150.1:p.Trp759Ter
  • NC_000023.10:g.18637987G>A
Protein change:
W759*
Molecular consequence:
  • NM_001037343.2:c.2277G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001323289.2:c.2277G>A - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003159.3:c.2277G>A - 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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV004591661Labcorp Genetics (formerly Invitae), Labcorp
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Pathogenic
(Nov 23, 2022) 		germlineclinical testing

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

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

CDKL5 variants: Improving our understanding of a rare neurologic disorder.

Hector RD, Kalscheuer VM, Hennig F, Leonard H, Downs J, Clarke A, Benke TA, Armstrong J, Pineda M, Bailey MES, Cobb SR.

Neurol Genet. 2017 Dec;3(6):e200. doi: 10.1212/NXG.0000000000000200.

PubMed [citation]
PMID:
29264392
PMCID:
PMC5732004

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, SCV004591661.1

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

Description

This premature translational stop signal has been observed in individual(s) with CDKL5-related conditions (PMID: 29264392). This variant is not present in population databases (gnomAD no frequency). This sequence change creates a premature translational stop signal (p.Trp759*) 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.

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

Last Updated: Sep 29, 2024