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NM_172107.4(KCNQ2):c.2330_2331dup (p.Glu778fs) AND Developmental and epileptic encephalopathy, 7

Germline classification:
Pathogenic (1 submission)
Last evaluated:
Jun 24, 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:
RCV003225700.2

Allele description [Variation Report for NM_172107.4(KCNQ2):c.2330_2331dup (p.Glu778fs)]

NM_172107.4(KCNQ2):c.2330_2331dup (p.Glu778fs)

Gene:
KCNQ2:potassium voltage-gated channel subfamily Q member 2 [Gene - OMIM - HGNC]
Variant type:
Duplication
Cytogenetic location:
20q13.33
Genomic location:
Preferred name:
NM_172107.4(KCNQ2):c.2330_2331dup (p.Glu778fs)
HGVS:
  • NC_000020.11:g.63406936_63406937dup
  • NG_009004.2:g.70708_70709dup
  • NM_001382235.1:c.2384_2385dup
  • NM_004518.6:c.2246_2247dup
  • NM_172106.3:c.2276_2277dup
  • NM_172107.4:c.2330_2331dupMANE SELECT
  • NM_172108.5:c.2237_2238dup
  • NP_001369164.1:p.Glu796fs
  • NP_004509.2:p.Glu750fs
  • NP_742104.1:p.Glu760fs
  • NP_742105.1:p.Glu778fs
  • NP_742106.1:p.Glu747fs
  • NC_000020.10:g.62038289_62038290dup
  • NM_172107.3:c.2330_2331dupCC
Protein change:
E747fs
Molecular consequence:
  • NM_001382235.1:c.2384_2385dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_004518.6:c.2246_2247dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_172106.3:c.2276_2277dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_172107.4:c.2330_2331dup - frameshift variant - [Sequence Ontology: SO:0001589]
  • NM_172108.5:c.2237_2238dup - frameshift variant - [Sequence Ontology: SO:0001589]

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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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003921997Victorian Clinical Genetics Services, Murdoch Childrens Research Institute

See additional submitters

criteria provided, single submitter

(ACMG Guidelines, 2015)		Pathogenic
(Jun 24, 2022) 		germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

Variable clinical expression in patients with mosaicism for KCNQ2 mutations.

Milh M, Lacoste C, Cacciagli P, Abidi A, Sutera-Sardo J, Tzelepis I, Colin E, Badens C, Afenjar A, Coeslier AD, Dailland T, Lesca G, Philip N, Villard L.

Am J Med Genet A. 2015 Oct;167A(10):2314-8. doi: 10.1002/ajmg.a.37152. Epub 2015 May 10.

PubMed [citation]
PMID:
25959266

Characteristics of KCNQ2 variants causing either benign neonatal epilepsy or developmental and epileptic encephalopathy.

Goto A, Ishii A, Shibata M, Ihara Y, Cooper EC, Hirose S.

Epilepsia. 2019 Sep;60(9):1870-1880. doi: 10.1111/epi.16314. Epub 2019 Aug 16.

PubMed [citation]
PMID:
31418850
See all PubMed Citations (3)

Details of each submission

From Victorian Clinical Genetics Services, Murdoch Childrens Research Institute, SCV003921997.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)

Description

Based on the classification scheme VCGS_Germline_v1.3.4, this variant is classified as Pathogenic. Following criteria are met: 0103 - Dominant negative and loss of function are known mechanisms of disease in this gene and are associated with developmental and epileptic encephalopathy 7 (MIM#613720) and benign neonatal seizures, 1 (MIM#121200), respectively (GeneReviews). There is currently no phenotypic correlation in terms of variant types or protein location (PMID: 31418850). (I) 0107 - This gene is associated with autosomal dominant disease. (I) 0112 - The condition associated with this gene has incomplete penetrance however, this is only reported for patients with benign neonatal seizures (PMID: 25959266). (I) 0208 - Variant is predicted to result in an elongated protein. (SP) 0251 - This variant is heterozygous. (I) 0301 - Variant is absent from gnomAD (both v2 and v3). (SP) 0701 - Other protein elongation variants comparable to the one identified in this case have very strong previous evidence for pathogenicity. More than five other similar protein elongation variants have been reported as pathogenic (ClinVar). (SP) 0807 - This variant has no previous evidence of pathogenicity. (I) 0905 - No published segregation evidence has been identified for this variant. (I) 1007 - No published functional evidence has been identified for this variant. (I) 1203 - This variant has been shown to be de novo in the proband (parental status confirmed) (by trio analysis). (SP) Legend: (SP) - Supporting pathogenic, (I) - Information, (SB) - Supporting benign

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Aug 4, 2024