NM_172107.4(KCNQ2):c.743_751del (p.Phe248_Val250del) AND Early infantile epileptic encephalopathy with suppression bursts

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Nov 4, 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:: RCV003588955.2

Allele description [Variation Report for NM_172107.4(KCNQ2):c.743_751del (p.Phe248_Val250del)]

NM_172107.4(KCNQ2):c.743_751del (p.Phe248_Val250del)

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.743_751del (p.Phe248_Val250del)

HGVS:

NC_000020.11:g.63442473_63442481del
NG_009004.2:g.35162_35170del
NM_001382235.1:c.743_751del
NM_004518.6:c.743_751del
NM_172106.3:c.743_751del
NM_172107.4:c.743_751delMANE SELECT
NM_172108.5:c.743_751del
NM_172109.3:c.743_751del
NP_001369164.1:p.Phe248_Val250del
NP_004509.2:p.Phe248_Val250del
NP_742104.1:p.Phe248_Val250del
NP_742105.1:p.Phe248_Val250del
NP_742106.1:p.Phe248_Val250del
NP_742107.1:p.Phe248_Val250del
NC_000020.10:g.62073824_62073832del
NC_000020.10:g.62073826_62073834del

Molecular consequence:

NM_001382235.1:c.743_751del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_004518.6:c.743_751del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172106.3:c.743_751del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172107.4:c.743_751del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172108.5:c.743_751del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_172109.3:c.743_751del - inframe_deletion - [Sequence Ontology: SO:0001822]

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
SCV004245982	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Nov 4, 2023)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27779742, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004245982

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Nov 4, 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

Gene mutation analysis of 175 Chinese patients with early-onset epileptic encephalopathy.

Zhang Q, Li J, Zhao Y, Bao X, Wei L, Wang J.

Clin Genet. 2017 May;91(5):717-724. doi: 10.1111/cge.12901. Epub 2017 Feb 16.

PubMed [citation]

PMID:: 27779742

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, SCV004245982.1

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

Description

This variant, c.743_751del, results in the deletion of 3 amino acid(s) of the KCNQ2 protein (p.Phe248_Val250del), but otherwise preserves the integrity of the reading frame. This variant is not present in population databases (gnomAD no frequency). This variant has not been reported in the literature in individuals affected with KCNQ2-related conditions. This variant disrupts a region of the KCNQ2 protein in which other variant(s) (p.Val250Leu) have been determined to be pathogenic (PMID: 27779742). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. For these reasons, this variant has been classified as Pathogenic.

#	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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