NM_001040142.2(SCN2A):c.606-159A>G AND Early infantile epileptic encephalopathy 11

Clinical significance:Pathogenic/Likely pathogenic (Last evaluated: Aug 28, 2018)

Review status:2 stars out of maximum of 4 stars

criteria provided, multiple submitters, no conflicts

Based on:
2 submissions [Details]
Record status:
current
Accession:
RCV000578189.2

Allele description [Variation Report for NM_001040142.2(SCN2A):c.606-159A>G]

NM_001040142.2(SCN2A):c.606-159A>G

Gene:
SCN2A:sodium voltage-gated channel alpha subunit 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q24.3
Genomic location:
Preferred name:
NM_001040142.2(SCN2A):c.606-159A>G
HGVS:
  • NC_000002.12:g.165309193A>G
  • NG_008143.1:g.74792A>G
  • NM_001040142.2:c.606-159A>GMANE SELECT
  • NM_001040143.2:c.634A>G
  • NM_001371246.1:c.634A>G
  • NM_001371247.1:c.606-159A>G
  • NM_021007.3:c.606-159A>G
  • NP_001035233.1:p.Asn212Asp
  • NP_001035233.1:p.Asn212Asp
  • NP_001358175.1:p.Asn212Asp
  • NC_000002.11:g.166165703A>G
  • NM_001040143.1:c.634A>G
Protein change:
N212D
Links:
dbSNP: rs1553567473
NCBI 1000 Genomes Browser:
rs1553567473
Molecular consequence:
  • NM_001040142.2:c.606-159A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001371247.1:c.606-159A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_021007.3:c.606-159A>G - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001040143.2:c.634A>G - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001371246.1:c.634A>G - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Early infantile epileptic encephalopathy 11 (DEE11)
Synonyms:
DEVELOPMENTAL AND EPILEPTIC ENCEPHALOPATHY 11
Identifiers:
MONDO: MONDO:0013388; MedGen: C3150987; Orphanet: 1934; OMIM: 613721

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000680024Victorian Clinical Genetics Services,Murdoch Childrens Research Institutecriteria provided, single submitter
Likely pathogenic
(Sep 11, 2017)
de novoclinical testing

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

SCV000966183Equipe Genetique des Anomalies du Developpement, Université de Bourgognecriteria provided, single submitter
Pathogenic
(Aug 28, 2018)
de novoclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedde novoyes11not provided3not providedclinical testing

Citations

PubMed

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 Victorian Clinical Genetics Services,Murdoch Childrens Research Institute, SCV000680024.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

A heterozygous missense variant was identified, NM_001040143.1(SCN2A):c.634A>G in exon 5 of the SCN2A gene (neonatal isoform). This substitution is predicted to create a minor amino acid change from an asparagine to an aspartic acid at position 212, NP_001035233.1(SCN2A):p.(Asn212Asp). The asparagine at this position has very high conservation (100 vertebrates, UCSC). In silico software predicts this variant to be disease causing (Polyphen, SIFT, Mutation Taster, CADD). It is situated in an ion transporter domain (within a linker region between two transmembrane segments). It is not present in the gnomAD population database and it has been previously reported in a patient with Ohtahara syndrome as a de novo event (Nakamura, K. et al. (2013)). Subsequent testing of parental samples indiciated this variant is due to a de novo event. Based on current information, this variant has been classified as LIKELY PATHOGENIC.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyes3Bloodnot provided1not provided1not provided

From Equipe Genetique des Anomalies du Developpement, Université de Bourgogne, SCV000966183.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1de novoyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Nov 20, 2021

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