rs997508

Positions:

• chr2-165309946-C-T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040142.2(SCN2A):​c.698-377C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.566 in 151,942 control chromosomes in the GnomAD database, including 24,858 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 0.57 (24858 hom., cov: 33)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.943

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=-0.91).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.617 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.698-377C>T		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.698-377C>T		intron_variant		ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.698-377C>T		intron_variant		5	NM_001040142.2	ENSP00000364586	P1
SCN2A	ENST00000631182.3	c.698-377C>T		intron_variant		5	NM_001371246.1	ENSP00000486885

Frequencies

GnomAD3 genomes AF: 0.566 AC: 85922 AN: 151826 Hom.: 24848 Cov.: 33

Gnomad AFR AF: 0.624

Gnomad AMI AF: 0.413

Gnomad AMR AF: 0.494

Gnomad ASJ AF: 0.633

Gnomad EAS AF: 0.294

Gnomad SAS AF: 0.486

Gnomad FIN AF: 0.471

Gnomad MID AF: 0.652

Gnomad NFE AF: 0.586

Gnomad OTH AF: 0.567

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

GnomAD4 genome AF: 0.566 AC: 85963 AN: 151942 Hom.: 24858 Cov.: 33 AF XY: 0.558 AC XY: 41410 AN XY: 74266

Gnomad4 AFR AF: 0.624

Gnomad4 AMR AF: 0.494

Gnomad4 ASJ AF: 0.633

Gnomad4 EAS AF: 0.294

Gnomad4 SAS AF: 0.486

Gnomad4 FIN AF: 0.471

Gnomad4 NFE AF: 0.586

Gnomad4 OTH AF: 0.561

Alfa AF: 0.566 Hom.: 3100

Bravo AF: 0.568

Asia WGS AF: 0.383 AC: 1336 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.44
DANN	Benign	0.53

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: rs997508; hg19: chr2-166166456;