rs12467383

Variant names:

• chr2-165369259-G-A
• rs12467383
• NM_001040142.2:c.3676-867G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-165369259-G-A
• chr2-165369259-G-C
• chr2-165369259-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040142.2(SCN2A):​c.3676-867G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.207 in 152,028 control chromosomes in the GnomAD database, including 3,960 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.21 (3960 hom., cov: 31)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.409
• Publications: 3 publications found

Genes affected

SCN2A (HGNC:10588): (sodium voltage-gated channel alpha subunit 2) Voltage-gated sodium channels are transmembrane glycoprotein complexes composed of a large alpha subunit with four repeat domains, each of which is composed of six membrane-spanning segments, and one or more regulatory beta subunits. Voltage-gated sodium channels function in the generation and propagation of action potentials in neurons and muscle. This gene encodes one member of the sodium channel alpha subunit gene family. Allelic variants of this gene are associated with seizure disorders and autism spectrum disorder. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Nov 2016]

SCN2A Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• developmental and epileptic encephalopathy, 11

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• episodic ataxia, type 9

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• seizures, benign familial infantile, 3

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• benign familial infantile epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• benign familial neonatal-infantile seizures

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Dravet syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• malignant migrating partial seizures of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.9).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.327 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001040142.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN2A	NM_001040142.2	MANE Select	c.3676-867G>A		intron	N/A	NP_001035232.1
	SCN2A	NM_001371246.1	MANE Plus Clinical	c.3676-867G>A		intron	N/A	NP_001358175.1
	SCN2A	NM_001040143.2		c.3676-867G>A		intron	N/A	NP_001035233.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN2A	ENST00000375437.7	TSL:5 MANE Select	c.3676-867G>A		intron	N/A	ENSP00000364586.2
	SCN2A	ENST00000631182.3	TSL:5 MANE Plus Clinical	c.3676-867G>A		intron	N/A	ENSP00000486885.1
	SCN2A	ENST00000283256.10	TSL:1	c.3676-867G>A		intron	N/A	ENSP00000283256.6

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31398 AN: 151910 Hom.: 3950 Cov.: 31

Gnomad AFR AF: 0.0644

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.211

Gnomad FIN AF: 0.310

Gnomad MID AF: 0.0823

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.207

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.207 AC: 31419 AN: 152028 Hom.: 3960 Cov.: 31 AF XY: 0.211 AC XY: 15653 AN XY: 74298

African (AFR) AF: 0.0642 AC: 2666 AN: 41514

American (AMR) AF: 0.297 AC: 4538 AN: 15262

Ashkenazi Jewish (ASJ) AF: 0.146 AC: 506 AN: 3468

East Asian (EAS) AF: 0.340 AC: 1746 AN: 5136

South Asian (SAS) AF: 0.210 AC: 1015 AN: 4822

European-Finnish (FIN) AF: 0.310 AC: 3265 AN: 10548

Middle Eastern (MID) AF: 0.0816 AC: 24 AN: 294

European-Non Finnish (NFE) AF: 0.249 AC: 16902 AN: 67958

Other (OTH) AF: 0.214 AC: 452 AN: 2114

Alfa AF: 0.131 Hom.: 267

Bravo AF: 0.202

Asia WGS AF: 0.275 AC: 953 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.56
PhyloP100		-0.41
Mutation Taster		=100/0	polymorphism (auto)

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs12467383; hg19: chr2-166225769;