rs2116658

Variant names:

• chr2-165310162-C-T
• rs2116658
• NM_001040142.2:c.698-161C>T

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Moderate BP6_Moderate BA1

The NM_001040142.2(SCN2A):​c.698-161C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.295 in 152,012 control chromosomes in the GnomAD database, including 6,911 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.29 (6911 hom., cov: 33)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.92

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=-0.31).
• BP6: Variant 2-165310162-C-T is Benign according to our data. Variant chr2-165310162-C-T is described in ClinVar as [Benign]. Clinvar id is 669359.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.307 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.698-161C>T		intron_variant	Intron 6 of 26	ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.698-161C>T		intron_variant	Intron 6 of 26	ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.698-161C>T		intron_variant	Intron 6 of 26	5	NM_001040142.2	ENSP00000364586.2
SCN2A	ENST00000631182.3	c.698-161C>T		intron_variant	Intron 6 of 26	5	NM_001371246.1	ENSP00000486885.1
SCN2A	ENST00000283256.10	c.698-161C>T		intron_variant	Intron 6 of 26	1		ENSP00000283256.6
SCN2A	ENST00000424833.5	c.698-161C>T		intron_variant	Intron 6 of 10	1		ENSP00000406454.2

Frequencies

GnomAD3 genomes AF: 0.295 AC: 44761 AN: 151896 Hom.: 6907 Cov.: 33

Gnomad AFR AF: 0.306

Gnomad AMI AF: 0.263

Gnomad AMR AF: 0.304

Gnomad ASJ AF: 0.458

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.295

Gnomad FIN AF: 0.143

Gnomad MID AF: 0.459

Gnomad NFE AF: 0.311

Gnomad OTH AF: 0.332

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

GnomAD4 genome AF: 0.295 AC: 44770 AN: 152012 Hom.: 6911 Cov.: 33 AF XY: 0.288 AC XY: 21370 AN XY: 74322

Gnomad4 AFR AF: 0.306

Gnomad4 AMR AF: 0.304

Gnomad4 ASJ AF: 0.458

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.294

Gnomad4 FIN AF: 0.143

Gnomad4 NFE AF: 0.311

Gnomad4 OTH AF: 0.329

Alfa AF: 0.306 Hom.: 3381

Bravo AF: 0.306

Asia WGS AF: 0.208 AC: 724 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jun 14, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	-0.31
CADD	Benign	18
DANN	Benign	0.77

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: rs2116658; hg19: chr2-166166672;