NM_001040142.2(SCN2A):c.658A>G (p.Arg220Gly) AND multiple conditions

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Sep 30, 2021
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:: RCV000688129.8

Allele description [Variation Report for NM_001040142.2(SCN2A):c.658A>G (p.Arg220Gly)]

NM_001040142.2(SCN2A):c.658A>G (p.Arg220Gly)

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.658A>G (p.Arg220Gly)

HGVS:

NC_000002.12:g.165309404A>G
NG_008143.1:g.75003A>G
NM_001040142.2:c.658A>GMANE SELECT
NM_001040143.2:c.697+148A>G
NM_001371246.1:c.697+148A>G
NM_001371247.1:c.658A>G
NM_021007.3:c.658A>G
NP_001035232.1:p.Arg220Gly
NP_001358176.1:p.Arg220Gly
NP_066287.2:p.Arg220Gly
NP_066287.2:p.Arg220Gly
NC_000002.11:g.166165914A>G
NM_021007.2:c.658A>G

Protein change:

R220G

Links:

dbSNP: rs1559352550

NCBI 1000 Genomes Browser:

rs1559352550

Molecular consequence:

NM_001040143.2:c.697+148A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001371246.1:c.697+148A>G - intron variant - [Sequence Ontology: SO:0001627]
NM_001040142.2:c.658A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001371247.1:c.658A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_021007.3:c.658A>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
SCV000815729	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Sep 30, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25818041, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000815729

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Sep 30, 2021)

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

Diagnostic yield of genetic testing in epileptic encephalopathy in childhood.

Mercimek-Mahmutoglu S, Patel J, Cordeiro D, Hewson S, Callen D, Donner EJ, Hahn CD, Kannu P, Kobayashi J, Minassian BA, Moharir M, Siriwardena K, Weiss SK, Weksberg R, Snead OC 3rd.

Epilepsia. 2015 May;56(5):707-16. doi: 10.1111/epi.12954. Epub 2015 Mar 25.

PubMed [citation]

PMID:: 25818041

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, SCV000815729.7

#	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"). This missense change has been observed in individual(s) with early infantile epileptic encephalopathy (PMID: 25818041; Invitae). In at least one individual the variant was observed to be de novo. This variant is not present in population databases (ExAC no frequency). This sequence change replaces arginine with glycine at codon 220 of the SCN2A protein (p.Arg220Gly). The arginine residue is highly conserved and there is a moderate physicochemical difference between arginine and glycine.

#	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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