NM_172107.4(KCNQ2):c.1962_1963del (p.Glu654fs) AND Inborn genetic diseases

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Aug 23, 2019
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:: RCV002421762.2

Allele description [Variation Report for NM_172107.4(KCNQ2):c.1962_1963del (p.Glu654fs)]

NM_172107.4(KCNQ2):c.1962_1963del (p.Glu654fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

20q13.33

Genomic location:

Preferred name:

NM_172107.4(KCNQ2):c.1962_1963del (p.Glu654fs)

HGVS:

NC_000020.11:g.63407301CT[1]
NG_009004.2:g.70338GA[1]
NM_001382235.1:c.2016_2017del
NM_004518.6:c.1878_1879del
NM_172106.3:c.1908_1909del
NM_172107.4:c.1962_1963delMANE SELECT
NM_172108.5:c.1869_1870del
NP_001369164.1:p.Glu672fs
NP_004509.2:p.Glu626fs
NP_742104.1:p.Glu636fs
NP_742105.1:p.Glu654fs
NP_742106.1:p.Glu623fs
NC_000020.10:g.62038654CT[1]
NM_172107.2:c.1962_1963delGA

Protein change:

E623fs

Molecular consequence:

NM_001382235.1:c.2016_2017del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004518.6:c.1878_1879del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172106.3:c.1908_1909del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172107.4:c.1962_1963del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_172108.5:c.1869_1870del - frameshift variant - [Sequence Ontology: SO:0001589]

Condition(s)

Name:: Inborn genetic diseases
Identifiers:: MeSH: D030342; MedGen: C0950123

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002721450	Ambry Genetics	criteria provided, single submitter (Ambry Variant Classification Scheme 2023)	Likely pathogenic (Aug 23, 2019)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002721450

Ambry Genetics

criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)

Likely pathogenic
(Aug 23, 2019)

germline

clinical testing

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

Citation Link

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

Diagnostic outcomes for genetic testing of 70 genes in 8565 patients with epilepsy and neurodevelopmental disorders.

Lindy AS, Stosser MB, Butler E, Downtain-Pickersgill C, Shanmugham A, Retterer K, Brandt T, Richard G, McKnight DA.

Epilepsia. 2018 May;59(5):1062-1071. doi: 10.1111/epi.14074. Epub 2018 Apr 14.

PubMed [citation]

PMID:: 29655203

Details of each submission

From Ambry Genetics, SCV002721450.2

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

Description

The c.1962_1963delGA variant, located in coding exon 17 of the KCNQ2 gene, results from a deletion of two nucleotides at nucleotide positions 1962 to 1963, causing a translational frameshift with a predicted alternate stop codon (p.E654Dfs*210). Frameshifts are typically deleterious in nature, however, this frameshift occurs at the 3' terminus of and is not expected to trigger nonsense-mediated mRNA decay. The exact functional impact of these altered amino acids is unknown at this time; however, similar frameshifts have been reported in a cohort of epilepsy an neurodevelopmental disorder patients (Lindy AS et al. Epilepsia, 2018 05;59:1062-1071). Based on the majority of available evidence to date, this variant is likely to be 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: May 1, 2024

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