NM_001323289.2(CDKL5):c.2684C>T (p.Pro895Leu) AND multiple conditions

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: May 16, 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:: RCV003774883.2

Allele description [Variation Report for NM_001323289.2(CDKL5):c.2684C>T (p.Pro895Leu)]

NM_001323289.2(CDKL5):c.2684C>T (p.Pro895Leu)

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.2684C>T (p.Pro895Leu)

Other names:

NM_001323289.2(CDKL5):c.2684C>T; p.Pro895Leu

HGVS:

NC_000023.11:g.18628558C>T
NG_008475.1:g.207954C>T
NM_001037343.2:c.2684C>T
NM_001323289.2:c.2684C>TMANE SELECT
NM_003159.2:c.2684C>T
NM_003159.3:c.2684C>T
NP_001032420.1:p.Pro895Leu
NP_001310218.1:p.Pro895Leu
NP_003150.1:p.Pro895Leu
NC_000023.10:g.18646678C>T
NM_001323289.2:c.2684C>T

Protein change:

P895L

Links:

dbSNP: rs587783157

NCBI 1000 Genomes Browser:

rs587783157

Molecular consequence:

NM_001037343.2:c.2684C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_001323289.2:c.2684C>T - missense variant - [Sequence Ontology: SO:0001583]
NM_003159.3:c.2684C>T - missense variant - [Sequence Ontology: SO:0001583]

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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004574753	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (May 16, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27770071, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004574753

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(May 16, 2023)

germline

clinical testing

PubMed (2)
[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

Seizure variables and their relationship to genotype and functional abilities in the CDKL5 disorder.

Fehr S, Wong K, Chin R, Williams S, de Klerk N, Forbes D, Krishnaraj R, Christodoulou J, Downs J, Leonard H.

Neurology. 2016 Nov 22;87(21):2206-2213. Epub 2016 Oct 21.

PubMed [citation]

PMID:: 27770071

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. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV004574753.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is not expected to disrupt CDKL5 protein function. ClinVar contains an entry for this variant (Variation ID: 1701032). This missense change has been observed in individual(s) with clinical features of CDKL5-related conditions (PMID: 27770071). This variant is present in population databases (rs587783157, gnomAD 0.02%). This sequence change replaces proline, which is neutral and non-polar, with leucine, which is neutral and non-polar, at codon 895 of the CDKL5 protein (p.Pro895Leu).

#	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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