NM_172107.4(KCNQ2):c.2102_2104del (p.Phe701del) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jun 18, 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:: RCV000545156.7

Allele description [Variation Report for NM_172107.4(KCNQ2):c.2102_2104del (p.Phe701del)]

NM_172107.4(KCNQ2):c.2102_2104del (p.Phe701del)

Gene:

KCNQ2:potassium voltage-gated channel subfamily Q member 2 [Gene - OMIM - HGNC]

Variant type:

Deletion

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_172107.4(KCNQ2):c.2102_2104del (p.Phe701del)

HGVS:

NC_000020.11:g.63407161_63407163del
NG_009004.2:g.70480_70482del
NM_004518.6:c.2018_2020del
NM_172106.3:c.2048_2050del
NM_172107.4:c.2102_2104delMANE SELECT
NM_172108.5:c.2009_2011del
NP_004509.2:p.Phe673del
NP_742104.1:p.Phe683del
NP_742105.1:p.Phe701del
NP_742106.1:p.Phe670del
NC_000020.10:g.62038512_62038514del
NC_000020.10:g.62038514_62038516del
NM_172107.2:c.2102_2104delTCT
NM_172107.4:c.2101_2103delTTCMANE SELECT
p.F701del

Protein change:

F670del

Links:

dbSNP: rs758334927

NCBI 1000 Genomes Browser:

rs758334927

Molecular consequence:

NM_004518.6:c.2018_2020del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172106.3:c.2048_2050del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172107.4:c.2102_2104del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172108.5:c.2009_2011del - inframe_deletion - [Sequence Ontology: SO:0001822]

Functional consequence:

Mild decrease in peak current [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0085]
Moderate slowing of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0014]
Normal voltage dependence of activation [Functional Epilepsy Nomenclature for Ion Channels: FENICS-0032]

Condition(s)

Name:: Early infantile epileptic encephalopathy with suppression bursts (EIEE)
Synonyms:: Early infantile epileptic encephalopathy; Ohtahara syndrome; Developmental and epileptic encephalopathy
Identifiers:: MONDO: MONDO:0100062; MedGen: C0393706; Orphanet: 1934; OMIM: PS308350

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000634058	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jun 18, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 35104249, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000634058

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jun 18, 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

High-throughput evaluation of epilepsy-associated KCNQ2 variants reveals functional and pharmacological heterogeneity.

Vanoye CG, Desai RR, Ji Z, Adusumilli S, Jairam N, Ghabra N, Joshi N, Fitch E, Helbig KL, McKnight D, Lindy AS, Zou F, Helbig I, Cooper EC, George AL Jr.

JCI Insight. 2022 Mar 8;7(5). doi:pii: e156314. 10.1172/jci.insight.156314.

PubMed [citation]

PMID:: 35104249
PMCID:: PMC8983144

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 Invitae, SCV000634058.4

#	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. Experimental studies are conflicting or provide insufficient evidence to determine the effect of this variant on KCNQ2 function (PMID: 35104249). Algorithms developed to predict the effect of variants on protein structure and function are not available or were not evaluated for this variant. ClinVar contains an entry for this variant (Variation ID: 205944). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. This variant is present in population databases (rs758334927, gnomAD 0.002%). This variant, c.2102_2104del, results in the deletion of 1 amino acid(s) of the KCNQ2 protein (p.Phe701del), but otherwise preserves the integrity of the reading frame.

#	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: Apr 15, 2024

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