NM_172107.4(KCNQ2):c.2321_2322delinsAT (p.Cys774Tyr) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Oct 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:: RCV001060631.9

Allele description [Variation Report for NM_172107.4(KCNQ2):c.2321_2322delinsAT (p.Cys774Tyr)]

NM_172107.4(KCNQ2):c.2321_2322delinsAT (p.Cys774Tyr)

Gene:

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

Variant type:

Indel

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_172107.4(KCNQ2):c.2321_2322delinsAT (p.Cys774Tyr)

HGVS:

NC_000020.11:g.63406941_63406942delinsAT
NG_009004.2:g.70699_70700delinsAT
NM_004518.6:c.2237_2238delinsAT
NM_172106.3:c.2267_2268delinsAT
NM_172107.4:c.2321_2322delinsATMANE SELECT
NM_172108.5:c.2228_2229delinsAT
NP_004509.2:p.Cys746Tyr
NP_742104.1:p.Cys756Tyr
NP_742105.1:p.Cys774Tyr
NP_742106.1:p.Cys743Tyr
NC_000020.10:g.62038294_62038295delinsAT
NM_172107.2:c.2321_2322delinsAT

Protein change:

C743Y

Links:

dbSNP: rs2079958591

NCBI 1000 Genomes Browser:

rs2079958591

Molecular consequence:

NM_004518.6:c.2237_2238delinsAT - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.2267_2268delinsAT - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.2321_2322delinsAT - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.2228_2229delinsAT - missense variant - [Sequence Ontology: SO:0001583]

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
SCV001225335	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Oct 18, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001225335

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Oct 18, 2023)

germline

clinical testing

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

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

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, SCV001225335.4

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

Description

This sequence change replaces cysteine, which is neutral and slightly polar, with tyrosine, which is neutral and polar, at codon 774 of the KCNQ2 protein (p.Cys774Tyr). This variant is present in population databases (no rsID available, gnomAD 0.003%). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. ClinVar contains an entry for this variant (Variation ID: 855374). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant¬†is likely to be tolerated. 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.

#	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: Sep 29, 2024

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