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NM_001323289.2(CDKL5):c.1523T>C (p.Ile508Thr) AND CDKL5 disorder

Germline classification:
Benign (2 submissions)
Last evaluated:
Aug 25, 2022
Review status:
3 stars out of maximum of 4 stars
reviewed by expert panel
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:
RCV002281060.3

Allele description [Variation Report for NM_001323289.2(CDKL5):c.1523T>C (p.Ile508Thr)]

NM_001323289.2(CDKL5):c.1523T>C (p.Ile508Thr)

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.1523T>C (p.Ile508Thr)
Other names:
NM_001323289.2(CDKL5):c.1523T>C; p.Ile508Thr
HGVS:
  • NC_000023.11:g.18604447T>C
  • NG_008475.1:g.183843T>C
  • NM_001037343.2:c.1523T>C
  • NM_001323289.2:c.1523T>CMANE SELECT
  • NM_003159.3:c.1523T>C
  • NP_001032420.1:p.Ile508Thr
  • NP_001310218.1:p.Ile508Thr
  • NP_003150.1:p.Ile508Thr
  • NP_003150.1:p.Ile508Thr
  • NC_000023.10:g.18622567T>C
  • NM_003159.2:c.1523T>C
Protein change:
I508T
Links:
RettBASE (CDKL5): 121; dbSNP: rs201893287
NCBI 1000 Genomes Browser:
rs201893287
Molecular consequence:
  • NM_001037343.2:c.1523T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001323289.2:c.1523T>C - missense variant - [Sequence Ontology: SO:0001583]
  • NM_003159.3:c.1523T>C - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:
CDKL5 disorder
Identifiers:
MONDO: MONDO:0100039; MedGen: CN296942

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV002569933ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel
reviewed by expert panel

(ClinGen RettAS ACMG Specifications V2)		Benign
(Aug 25, 2022) 		germlinecuration

Citation Link,

SCV005335299Centre for Population Genomics, CPG
criteria provided, single submitter

(McKnight et al. (Hum Mutat. 2022))		Benign
(Jul 12, 2024) 		germlinecuration

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

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedcuration

Citations

PubMed

Recommendations by the ClinGen Rett/Angelman-like expert panel for gene-specific variant interpretation methods.

McKnight D, Bean L, Karbassi I, Beattie K, Bienvenu T, Bonin H, Fang P, Chrisodoulou J, Friez M, Helgeson M, Krishnaraj R, Meng L, Mighion L, Neul J, Percy A, Ramsden S, Zoghbi H, Das S.

Hum Mutat. 2022 Aug;43(8):1097-1113. doi: 10.1002/humu.24302. Epub 2021 Dec 2.

PubMed [citation]
PMID:
34837432
PMCID:
PMC9135956

Details of each submission

From ClinGen Rett and Angelman-like Disorders Variant Curation Expert Panel, SCV002569933.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcurationnot provided

Description

The allele frequency of the p.Ile508Thr variant in CDKL5 is 0.018% in European (Non-Finnish) sub population in gnomAD, which is high enough to be classified as likely benign based on thresholds defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like conditions (BS1). The p.Ile508Thr variant is observed in at least 2 unaffected individuals (internal database) (BS2). Computational analysis prediction tools suggest that the p.Ile508Thr variant does not have a deleterious impact; however this information does not predict clinical significance on its own (BP4). In summary, the p.Ile508Thr variant in CDKL5 is classified as benign based on the ACMG/AMP criteria (BS1, BS2, BP4).

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

From Centre for Population Genomics, CPG, SCV005335299.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedcuration PubMed (1)

Description

This variant has been collected from RettBASE and curated to current modified ACMG/AMP criteria. Based on the classification scheme defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders Specifications to the ACMG/AMP Variant Interpretation Guidelines VCEP 3.0, this variant is classified as benign. At least the following criteria are met: The allele frequency of this variant in at least one population in gnomAD is higher than the 0.03% threshold defined by the ClinGen Rett/Angelman-like Expert Panel for Rett/AS-like Disorders VCEP 3.0 (BA1).

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

Last Updated: Nov 10, 2024