rs10184275

Positions:

• chr2-165271418-G-A
• chr2-165271418-G-C
• chr2-165271418-G-T

Variant summary

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

The NM_001040142.2(SCN2A):​c.-51-24355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,044 control chromosomes in the GnomAD database, including 56,229 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 0.86 (56224 hom., cov: 31)
  • Exomes 𝑓: 0.78 (5 hom.)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770

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=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-24355G>A		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-24355G>A		intron_variant		ENST00000631182.3	NP_001358175.1
SCN2A	NM_001040143.2	c.-51-24355G>A		intron_variant			NP_001035233.1
SCN2A	NM_001371247.1	c.-51-24355G>A		intron_variant			NP_001358176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.-51-24355G>A		intron_variant		5	NM_001040142.2	ENSP00000364586	P1
SCN2A	ENST00000631182.3	c.-51-24355G>A		intron_variant		5	NM_001371246.1	ENSP00000486885

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130142 AN: 151908 Hom.: 56169 Cov.: 31

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.862

GnomAD4 exome AF: 0.778 AC: 14 AN: 18 Hom.: 5 Cov.: 0 AF XY: 0.813 AC XY: 13 AN XY: 16

Gnomad4 EAS exome AF: 0.500

Gnomad4 FIN exome AF: 0.500

Gnomad4 NFE exome AF: 0.857

GnomAD4 genome AF: 0.857 AC: 130252 AN: 152026 Hom.: 56224 Cov.: 31 AF XY: 0.855 AC XY: 63528 AN XY: 74318

Gnomad4 AFR AF: 0.961

Gnomad4 AMR AF: 0.846

Gnomad4 ASJ AF: 0.877

Gnomad4 EAS AF: 0.770

Gnomad4 SAS AF: 0.819

Gnomad4 FIN AF: 0.793

Gnomad4 NFE AF: 0.815

Gnomad4 OTH AF: 0.862

Alfa AF: 0.830 Hom.: 24904

Bravo AF: 0.867

Asia WGS AF: 0.822 AC: 2859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
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: rs10184275; hg19: chr2-166127928;