NM_172107.4(KCNQ2):c.569A>T (p.Asn190Ile) AND Developmental and epileptic encephalopathy, 7

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Mar 22, 2022
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:: RCV002052179.1

Allele description [Variation Report for NM_172107.4(KCNQ2):c.569A>T (p.Asn190Ile)]

NM_172107.4(KCNQ2):c.569A>T (p.Asn190Ile)

Gene:

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

Variant type:

single nucleotide variant

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_172107.4(KCNQ2):c.569A>T (p.Asn190Ile)

HGVS:

NC_000020.11:g.63444780T>A
NG_009004.2:g.32861A>T
NM_001382235.1:c.569A>T
NM_004518.6:c.569A>T
NM_172106.3:c.569A>T
NM_172107.4:c.569A>TMANE SELECT
NM_172108.5:c.569A>T
NM_172109.3:c.569A>T
NP_001369164.1:p.Asn190Ile
NP_004509.2:p.Asn190Ile
NP_742104.1:p.Asn190Ile
NP_742105.1:p.Asn190Ile
NP_742106.1:p.Asn190Ile
NP_742107.1:p.Asn190Ile
NC_000020.10:g.62076133T>A

Protein change:

N190I

Links:

dbSNP: rs2145775795

NCBI 1000 Genomes Browser:

rs2145775795

Molecular consequence:

NM_001382235.1:c.569A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_004518.6:c.569A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172106.3:c.569A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172107.4:c.569A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172108.5:c.569A>T - missense variant - [Sequence Ontology: SO:0001583]
NM_172109.3:c.569A>T - missense variant - [Sequence Ontology: SO:0001583]

Observations:

Condition(s)

Name:: Developmental and epileptic encephalopathy, 7 (DEE7)
Synonyms:: Early infantile epileptic encephalopathy 7; KCNQ2-Related Neonatal Epileptic Encephalopathy
Identifiers:: MONDO: MONDO:0013387; MedGen: C3150986; Orphanet: 439218; OMIM: 613720

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002318710	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain significance (Mar 22, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 27602407, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002318710

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain significance
(Mar 22, 2022)

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	yes	1	not provided	not provided	1	not provided	clinical testing

Citations

PubMed

KCNQ2 encephalopathy: Features, mutational hot spots, and ezogabine treatment of 11 patients.

Millichap JJ, Park KL, Tsuchida T, Ben-Zeev B, Carmant L, Flamini R, Joshi N, Levisohn PM, Marsh E, Nangia S, Narayanan V, Ortiz-Gonzalez XR, Patterson MC, Pearl PL, Porter B, Ramsey K, McGinnis EL, Taglialatela M, Tracy M, Tran B, Venkatesan C, Weckhuysen S, et al.

Neurol Genet. 2016 Oct;2(5):e96. doi: 10.1212/NXG.0000000000000096.

PubMed [citation]

PMID:: 27602407
PMCID:: PMC4995058

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From 3billion, SCV002318710.1

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

Description

Different pathogenic/likely pathogenic amino acid change has been reported with supporting evidence at the same codon (PMID:27602407). In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.881>=0.6, 3CNET: 0.994>=0.75). A missense variant is a common mechanism. It is not observed in the gnomAD v2.1.1 dataset. Therefore, this variant is classified as uncertain significance according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	yes	1	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Dec 24, 2023

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