NM_001040142.2(SCN2A):c.647T>C (p.Leu216Ser) AND Developmental and epileptic encephalopathy, 11

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Feb 23, 2023
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:: RCV003152837.1

Allele description [Variation Report for NM_001040142.2(SCN2A):c.647T>C (p.Leu216Ser)]

NM_001040142.2(SCN2A):c.647T>C (p.Leu216Ser)

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>C (p.Leu216Ser)

HGVS:

NC_000002.12:g.165309393T>C
NG_008143.1:g.74992T>C
NM_001040142.2:c.647T>CMANE SELECT
NM_001040143.2:c.697+137T>C
NM_001371246.1:c.697+137T>C
NM_001371247.1:c.647T>C
NM_021007.3:c.647T>C
NP_001035232.1:p.Leu216Ser
NP_001358176.1:p.Leu216Ser
NP_066287.2:p.Leu216Ser
NC_000002.11:g.166165903T>C

Protein change:

L216S

Molecular consequence:

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

Condition(s)

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

Recent activity

Clear Turn Off Turn On

Homo sapiens HDGF like 1 (HDGFL1), mRNA
Homo sapiens HDGF like 1 (HDGFL1), mRNA
gi|1050115285|ref|NM_138574.3|

Nucleotide

Your browsing activity is empty.

Activity recording is turned off.

Turn recording back on

Help

Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV003841290	3billion	criteria provided, single submitter (ACMG Guidelines, 2015)	Likely pathogenic (Feb 23, 2023)	unknown	clinical testing	PubMed (2) [See all records that cite these PMIDs] 30109124, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV003841290

3billion

criteria provided, single submitter

(ACMG Guidelines, 2015)

Likely pathogenic
(Feb 23, 2023)

unknown

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	unknown	yes	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

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 3billion, SCV003841290.1

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

Description

The variant is not observed in the gnomAD v2.1.1 dataset. The variant is located in a mutational hot spot and/or well-established functional domain in which established pathogenic variants have been reported. In silico tool predictions suggest damaging effect of the variant on gene or gene product (REVEL: 0.89; 3Cnet: 1.00). A different missense change at the same codon (p.Leu216Trp) has been reported as pathogenic/likely pathogenic with strong evidence (ClinVar ID: VCV000207088 / PMID: 30109124). Therefore, this variant is classified as Likely pathogenic according to the recommendation of ACMG/AMP guideline.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	unknown	yes	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Aug 5, 2023

ClinVar

Relating variation to medicine