rs3943809

Positions:

• chr2-165344371-A-G

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_001040142.2(SCN2A):​c.2563-184A>G 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 151,940 control chromosomes in the GnomAD database, including 3,971 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.21 (3971 hom., cov: 32)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0240

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.82).
• BP6: Variant 2-165344371-A-G is Benign according to our data. Variant chr2-165344371-A-G is described in ClinVar as [Benign]. Clinvar id is 669324.Status of the report is criteria_provided_single_submitter, 1 stars.
• 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/exons	MANE	UniProt
SCN2A	NM_001040142.2	c.2563-184A>G		intron_variant		ENST00000375437.7
SCN2A	NM_001371246.1	c.2563-184A>G		intron_variant		ENST00000631182.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN2A	ENST00000375437.7	c.2563-184A>G		intron_variant		5	NM_001040142.2	P1
SCN2A	ENST00000631182.3	c.2563-184A>G		intron_variant		5	NM_001371246.1

Frequencies

GnomAD3 genomes AF: 0.207 AC: 31408 AN: 151826 Hom.: 3961 Cov.: 32

Gnomad AFR AF: 0.0647

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.297

Gnomad ASJ AF: 0.146

Gnomad EAS AF: 0.340

Gnomad SAS AF: 0.212

Gnomad FIN AF: 0.308

Gnomad MID AF: 0.0791

Gnomad NFE AF: 0.249

Gnomad OTH AF: 0.206

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

GnomAD4 genome AF: 0.207 AC: 31431 AN: 151940 Hom.: 3971 Cov.: 32 AF XY: 0.211 AC XY: 15656 AN XY: 74262

Gnomad4 AFR AF: 0.0646

Gnomad4 AMR AF: 0.297

Gnomad4 ASJ AF: 0.146

Gnomad4 EAS AF: 0.340

Gnomad4 SAS AF: 0.211

Gnomad4 FIN AF: 0.308

Gnomad4 NFE AF: 0.249

Gnomad4 OTH AF: 0.213

Alfa AF: 0.232 Hom.: 566

Bravo AF: 0.202

Asia WGS AF: 0.276 AC: 954 AN: 3466

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 14, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.82
CADD	Benign	1.3
DANN	Benign	0.72

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: rs3943809; hg19: chr2-166200881;