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NM_001323289.2(CDKL5):c.2842C>T (p.Arg948Ter) AND Developmental and epileptic encephalopathy, 2

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Sep 5, 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:
RCV000735202.3

Allele description [Variation Report for NM_001323289.2(CDKL5):c.2842C>T (p.Arg948Ter)]

NM_001323289.2(CDKL5):c.2842C>T (p.Arg948Ter)

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.2842C>T (p.Arg948Ter)
Other names:
NM_001323289.2(CDKL5):c.2842C>T; p.Arg948Ter
HGVS:
  • NC_000023.11:g.18628716C>T
  • NG_008475.1:g.208112C>T
  • NM_001037343.2:c.2713+129C>T
  • NM_001323289.2:c.2842C>TMANE SELECT
  • NM_003159.3:c.2713+129C>T
  • NP_001310218.1:p.Arg948Ter
  • NC_000023.10:g.18646836C>T
  • NM_001323289.1:c.2842C>T
  • NM_003159.2:c.2713+129C>T
Protein change:
R948*
Links:
dbSNP: rs1555955296
NCBI 1000 Genomes Browser:
rs1555955296
Molecular consequence:
  • NM_001037343.2:c.2713+129C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_003159.3:c.2713+129C>T - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001323289.2:c.2842C>T - nonsense - [Sequence Ontology: SO:0001587]
Observations:
1

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

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000863408Undiagnosed Diseases Network, NIH
criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Sep 5, 2018) 		de novoclinical testing

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
Whitede novoyes11not providednot providednot providedclinical testing

Citations

PubMed

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee.

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]
PMID:
25741868
PMCID:
PMC4544753

Details of each submission

From Undiagnosed Diseases Network, NIH, SCV000863408.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1White1not providednot providedclinical testing PubMed (1)

Description

This variant was reported by the clinical laboratory as pathogenic in July 2018. Previous testing at a different laboratory in October 2016 did not report the variant because it was only in a coding region on transcript NM_001323289.1 and not the other isoforms of CDKL5, including the canonical transcript. This transcript was added to NCBI RefSeq database in April 2016 but had not yet been curated into their annotation set and so was not included in their analysis in October 2016. This variant is present in the NM_001323289.1 transcript, which is confirmed to be expressed in the brain in both humans and mice. Our patient's variant is located in exon 17, which is longer in this alternative transcript than in the canonical transcript. Earlier this year, a male patient with intractable seizures was reported to have a de novo frameshift mutation within the same exon 17 in the same transcript NM_001323289.1 (PMID: 29444904).

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providedbloodnot provided1not provided1not provided

Last Updated: Dec 28, 2024