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. Variant got -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

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]

ACMG classification

Verdict is Benign. Variant got -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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.3676-867G>A		intron_variant	Intron 19 of 26	ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.3676-867G>A		intron_variant	Intron 19 of 26	ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.3676-867G>A		intron_variant	Intron 19 of 26	5	NM_001040142.2	ENSP00000364586.2
SCN2A	ENST00000631182.3	c.3676-867G>A		intron_variant	Intron 19 of 26	5	NM_001371246.1	ENSP00000486885.1
SCN2A	ENST00000283256.10	c.3676-867G>A		intron_variant	Intron 19 of 26	1		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

Gnomad4 AFR AF: 0.0642

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.210

Gnomad4 FIN AF: 0.310

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.214

Alfa AF: 0.134 Hom.: 267

Bravo AF: 0.202

Asia WGS AF: 0.275 AC: 953 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	0.75
DANN	Benign	0.56

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

Publications

LitVar

Other links and lift over

dbSNP: rs12467383; hg19: chr2-166225769;