2-165270773-C-T

Position:

• chr2-165270773-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.-51-25000C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.801 in 152,084 control chromosomes in the GnomAD database, including 49,220 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 0.80 (49181 hom., cov: 31)
  • Exomes 𝑓: 0.74 (39 hom.)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.952

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]

SCN2A (HGNC:):

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.92).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.878 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-25000C>T		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-25000C>T		intron_variant		ENST00000631182.3	NP_001358175.1
SCN2A	NM_001040143.2	c.-51-25000C>T		intron_variant			NP_001035233.1
SCN2A	NM_001371247.1	c.-51-25000C>T		intron_variant			NP_001358176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.-51-25000C>T		intron_variant		5	NM_001040142.2	ENSP00000364586.2
SCN2A	ENST00000631182.3	c.-51-25000C>T		intron_variant		5	NM_001371246.1	ENSP00000486885.1
SCN2A	ENST00000424833.5	c.-51-25000C>T		intron_variant		1		ENSP00000406454.2

Frequencies

GnomAD3 genomes AF: 0.801 AC: 121594 AN: 151824 Hom.: 49132 Cov.: 31

Gnomad AFR AF: 0.886

Gnomad AMI AF: 0.603

Gnomad AMR AF: 0.824

Gnomad ASJ AF: 0.804

Gnomad EAS AF: 0.771

Gnomad SAS AF: 0.754

Gnomad FIN AF: 0.685

Gnomad MID AF: 0.848

Gnomad NFE AF: 0.770

Gnomad OTH AF: 0.804

GnomAD4 exome AF: 0.739 AC: 105 AN: 142 Hom.: 39 Cov.: 0 AF XY: 0.750 AC XY: 60 AN XY: 80

Gnomad4 AFR exome AF: 1.00

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.707

Gnomad4 NFE exome AF: 0.760

Gnomad4 OTH exome AF: 1.00

GnomAD4 genome AF: 0.801 AC: 121698 AN: 151942 Hom.: 49181 Cov.: 31 AF XY: 0.797 AC XY: 59192 AN XY: 74248

Gnomad4 AFR AF: 0.886

Gnomad4 AMR AF: 0.823

Gnomad4 ASJ AF: 0.804

Gnomad4 EAS AF: 0.771

Gnomad4 SAS AF: 0.753

Gnomad4 FIN AF: 0.685

Gnomad4 NFE AF: 0.770

Gnomad4 OTH AF: 0.804

Alfa AF: 0.784 Hom.: 62339

Bravo AF: 0.817

Asia WGS AF: 0.792 AC: 2756 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.92
CADD	Benign	0.73
DANN	Benign	0.54

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: rs2119067; hg19: chr2-166127283;