NM_001040142.2(SCN2A):c.647T>G (p.Leu216Trp) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Feb 14, 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:: RCV001390241.8

Allele description [Variation Report for NM_001040142.2(SCN2A):c.647T>G (p.Leu216Trp)]

NM_001040142.2(SCN2A):c.647T>G (p.Leu216Trp)

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.647T>G (p.Leu216Trp)

Other names:

p.L216W:TTG>TGG

HGVS:

NC_000002.12:g.165309393T>G
NG_008143.1:g.74992T>G
NM_001040142.2:c.647T>GMANE SELECT
NM_001040143.2:c.697+137T>G
NM_001371246.1:c.697+137T>G
NM_001371247.1:c.647T>G
NM_021007.3:c.647T>G
NP_001035232.1:p.Leu216Trp
NP_001358176.1:p.Leu216Trp
NP_066287.2:p.Leu216Trp
NP_066287.2:p.Leu216Trp
NC_000002.11:g.166165903T>G
NM_021007.2:c.647T>G

Protein change:

L216W

Links:

dbSNP: rs796053203

NCBI 1000 Genomes Browser:

rs796053203

Molecular consequence:

NM_001040143.2:c.697+137T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001371246.1:c.697+137T>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001040142.2:c.647T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001371247.1:c.647T>G - missense variant - [Sequence Ontology: SO:0001583]
NM_021007.3:c.647T>G - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Name:: Seizures, benign familial infantile, 3 (BFIS3)
Synonyms:: CONVULSIONS, BENIGN FAMILIAL INFANTILE, 3; Familial neonatal seizures
Identifiers:: MONDO: MONDO:0011904; MedGen: C1843140; Orphanet: 140927; Orphanet: 306; OMIM: 607745

Name:: Developmental and epileptic encephalopathy, 11 (DEE11)
Synonyms:: Early infantile epileptic encephalopathy 11
Identifiers:: MONDO: MONDO:0013388; MedGen: C3150987; Orphanet: 1934; OMIM: 613721

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001591910	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Feb 14, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30109124, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001591910

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Feb 14, 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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Whole-genome analysis for effective clinical diagnosis and gene discovery in early infantile epileptic encephalopathy.

Ostrander BEP, Butterfield RJ, Pedersen BS, Farrell AJ, Layer RM, Ward A, Miller C, DiSera T, Filloux FM, Candee MS, Newcomb T, Bonkowsky JL, Marth GT, Quinlan AR.

NPJ Genom Med. 2018;3:22. doi: 10.1038/s41525-018-0061-8.

PubMed [citation]

PMID:: 30109124
PMCID:: PMC6089881

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, SCV001591910.5

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

Description

For these reasons, this variant has been classified as Pathogenic. Algorithms developed to predict the effect of missense changes on protein structure and function are either unavailable or do not agree on the potential impact of this missense change (SIFT: "Deleterious"; PolyPhen-2: "Probably Damaging"; Align-GVGD: "Class C0"). ClinVar contains an entry for this variant (Variation ID: 207088). This missense change has been observed in individual(s) with SCN2A-related conditions (PMID: 30109124; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces leucine, which is neutral and non-polar, with tryptophan, which is neutral and slightly polar, at codon 216 of the SCN2A protein (p.Leu216Trp).

#	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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