chr2-165268709-C-T

Position:

• chr2-165268709-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.-51-27064C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.379 in 151,484 control chromosomes in the GnomAD database, including 11,292 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 0.38 (11292 hom., cov: 30)
  • Exomes 𝑓: 0.20 (0 hom.)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.851

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=-1.04).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.475 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-27064C>T		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-27064C>T		intron_variant		ENST00000631182.3	NP_001358175.1
SCN2A	NM_001040143.2	c.-52+23261C>T		intron_variant			NP_001035233.1
SCN2A	NM_001371247.1	c.-51-27064C>T		intron_variant			NP_001358176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.-51-27064C>T		intron_variant		5	NM_001040142.2	ENSP00000364586	P1
SCN2A	ENST00000631182.3	c.-51-27064C>T		intron_variant		5	NM_001371246.1	ENSP00000486885

Frequencies

GnomAD3 genomes AF: 0.379 AC: 57424 AN: 151356 Hom.: 11274 Cov.: 30

Gnomad AFR AF: 0.480

Gnomad AMI AF: 0.395

Gnomad AMR AF: 0.429

Gnomad ASJ AF: 0.334

Gnomad EAS AF: 0.471

Gnomad SAS AF: 0.323

Gnomad FIN AF: 0.287

Gnomad MID AF: 0.347

Gnomad NFE AF: 0.320

Gnomad OTH AF: 0.388

GnomAD4 exome AF: 0.200 AC: 2 AN: 10 Hom.: 0 Cov.: 0 AF XY: 0.167 AC XY: 1 AN XY: 6

Gnomad4 FIN exome AF: 0.250

Gnomad4 NFE exome AF: 0.167

GnomAD4 genome AF: 0.380 AC: 57486 AN: 151474 Hom.: 11292 Cov.: 30 AF XY: 0.378 AC XY: 27945 AN XY: 74014

Gnomad4 AFR AF: 0.480

Gnomad4 AMR AF: 0.429

Gnomad4 ASJ AF: 0.334

Gnomad4 EAS AF: 0.471

Gnomad4 SAS AF: 0.322

Gnomad4 FIN AF: 0.287

Gnomad4 NFE AF: 0.320

Gnomad4 OTH AF: 0.393

Alfa AF: 0.335 Hom.: 17639

Bravo AF: 0.398

Asia WGS AF: 0.447 AC: 1553 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	2.4
DANN	Benign	0.79

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: rs10174400; hg19: chr2-166125219;