2-165293790-G-C

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.-51-1983G>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.243 in 968,570 control chromosomes in the GnomAD database, including 29,213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.23 (4469 hom., cov: 30)
  • Exomes 𝑓: 0.24 (24744 hom.)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.95

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=-0.86).
• BP6: Variant 2-165293790-G-C is Benign according to our data. Variant chr2-165293790-G-C is described in ClinVar as [Benign]. Clinvar id is 1245138.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.351 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN2A	NM_001040142.2	c.-51-1983G>C		intron_variant		ENST00000375437.7
SCN2A	NM_001371246.1	c.-51-1983G>C		intron_variant		ENST00000631182.3
SCN2A	NM_001040143.2	c.-51-1983G>C		intron_variant
SCN2A	NM_001371247.1	c.-51-1983G>C		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN2A	ENST00000375437.7	c.-51-1983G>C		intron_variant		5	NM_001040142.2	P1
SCN2A	ENST00000631182.3	c.-51-1983G>C		intron_variant		5	NM_001371246.1

Frequencies

GnomAD3 genomes AF: 0.235 AC: 35557 AN: 151460 Hom.: 4457 Cov.: 30

Gnomad AFR AF: 0.157

Gnomad AMI AF: 0.334

Gnomad AMR AF: 0.318

Gnomad ASJ AF: 0.137

Gnomad EAS AF: 0.364

Gnomad SAS AF: 0.236

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.250

Gnomad OTH AF: 0.232

GnomAD4 exome AF: 0.244 AC: 199637 AN: 816994 Hom.: 24744 Cov.: 14 AF XY: 0.244 AC XY: 92327 AN XY: 377940

Gnomad4 AFR exome AF: 0.139

Gnomad4 AMR exome AF: 0.314

Gnomad4 ASJ exome AF: 0.135

Gnomad4 EAS exome AF: 0.352

Gnomad4 SAS exome AF: 0.245

Gnomad4 FIN exome AF: 0.318

Gnomad4 NFE exome AF: 0.247

Gnomad4 OTH exome AF: 0.231

GnomAD4 genome AF: 0.235 AC: 35593 AN: 151576 Hom.: 4469 Cov.: 30 AF XY: 0.238 AC XY: 17610 AN XY: 74028

Gnomad4 AFR AF: 0.157

Gnomad4 AMR AF: 0.318

Gnomad4 ASJ AF: 0.137

Gnomad4 EAS AF: 0.365

Gnomad4 SAS AF: 0.236

Gnomad4 FIN AF: 0.284

Gnomad4 NFE AF: 0.250

Gnomad4 OTH AF: 0.239

Alfa AF: 0.246 Hom.: 608

Bravo AF: 0.236

Asia WGS AF: 0.306 AC: 1062 AN: 3478

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

May 20, 2019

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.17
Dann	Benign	0.37

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: rs12614399; hg19: chr2-166150300;