NM_001323289.2(CDKL5):c.1675C>T (p.Arg559Ter) AND multiple conditions

Clinical significance:Pathogenic (Last evaluated: Jul 3, 2018)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV000694251.1

Allele description [Variation Report for NM_001323289.2(CDKL5):c.1675C>T (p.Arg559Ter)]

NM_001323289.2(CDKL5):c.1675C>T (p.Arg559Ter)

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.1675C>T (p.Arg559Ter)
Other names:
p.R559*:CGA>TGA
HGVS:
  • NC_000023.11:g.18604599C>T
  • NG_008475.1:g.183995C>T
  • NM_001037343.1:c.1675C>T
  • NM_001037343.2:c.1675C>T
  • NM_001323289.2:c.1675C>TMANE SELECT
  • NM_003159.2:c.1675C>T
  • NM_003159.3:c.1675C>T
  • NP_001032420.1:p.Arg559Ter
  • NP_001032420.1:p.Arg559Ter
  • NP_001310218.1:p.Arg559Ter
  • NP_003150.1:p.Arg559Ter
  • NP_003150.1:p.Arg559Ter
  • NC_000023.10:g.18622719C>T
Protein change:
R559*
Links:
RettBASE (CDKL5): 86; dbSNP: rs267608395
NCBI 1000 Genomes Browser:
rs267608395
Molecular consequence:
  • NM_001037343.1:c.1675C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001037343.2:c.1675C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001323289.2:c.1675C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003159.2:c.1675C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_003159.3:c.1675C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:
Early infantile epileptic encephalopathy 2 (DEE2)
Synonyms:
INFANTILE SPASM SYNDROME, X-LINKED 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

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000822686Invitaecriteria provided, single submitter
Pathogenic
(Jul 3, 2018)
germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Summary from all submissions

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

Citations

PubMed

A novel CDKL5 mutation in a 47,XXY boy with the early-onset seizure variant of Rett syndrome.

Sartori S, Di Rosa G, Polli R, Bettella E, Tricomi G, Tortorella G, Murgia A.

Am J Med Genet A. 2009 Feb;149A(2):232-6. doi: 10.1002/ajmg.a.32606.

PubMed [citation]
PMID:
19161156

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From Invitae, SCV000822686.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

This sequence change creates a premature translational stop signal (p.Arg559*) in the CDKL5 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has been observed in individuals with epilepsy (PMID: 27770071, 27823948, 22872100) and to be de novo in an individual affected with suspected early onset encephalopathy (PMID: 19161156). ClinVar contains an entry for this variant (Variation ID: 143781). 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: Nov 20, 2021

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