chr2-165294040-AT-A

Variant names:

• chr2-165294040-AT-A
• rs1553563950
• ENST00000283256:c.-134delT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The ENST00000283256(SCN2A):​c.-134delT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.010 (9 hom., cov: 11)
  • Exomes 𝑓: 0.055 (2 hom.)
• Consequence: SCN2A ENST00000283256 5_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.275

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 -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.107 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-1720delT		intron_variant	Intron 1 of 26	ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-1720delT		intron_variant	Intron 1 of 26	ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000283256	c.-134delT		5_prime_UTR_variant	Exon 1 of 27	1		ENSP00000283256.6
SCN2A	ENST00000375437.7	c.-51-1720delT		intron_variant	Intron 1 of 26	5	NM_001040142.2	ENSP00000364586.2
SCN2A	ENST00000631182.3	c.-51-1720delT		intron_variant	Intron 1 of 26	5	NM_001371246.1	ENSP00000486885.1
SCN2A	ENST00000424833.5	c.-51-1720delT		intron_variant	Intron 1 of 10	1		ENSP00000406454.2

Frequencies

GnomAD3 genomes AF: 0.0102 AC: 1060 AN: 103596 Hom.: 9 Cov.: 11

Gnomad AFR AF: 0.0352

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00432

Gnomad ASJ AF: 0.000380

Gnomad EAS AF: 0.000302

Gnomad SAS AF: 0.000682

Gnomad FIN AF: 0.000869

Gnomad MID AF: 0.00526

Gnomad NFE AF: 0.000647

Gnomad OTH AF: 0.00595

GnomAD4 exome AF: 0.0552 AC: 27259 AN: 493646 Hom.: 2 Cov.: 0 AF XY: 0.0557 AC XY: 12774 AN XY: 229386

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0557

Gnomad4 ASJ exome AF: 0.0707

Gnomad4 EAS exome AF: 0.0292

Gnomad4 SAS exome AF: 0.0511

Gnomad4 FIN exome AF: 0.0407

Gnomad4 NFE exome AF: 0.0541

Gnomad4 OTH exome AF: 0.0580

GnomAD4 genome AF: 0.0102 AC: 1060 AN: 103632 Hom.: 9 Cov.: 11 AF XY: 0.0106 AC XY: 510 AN XY: 47900

Gnomad4 AFR AF: 0.0351

Gnomad4 AMR AF: 0.00431

Gnomad4 ASJ AF: 0.000380

Gnomad4 EAS AF: 0.000302

Gnomad4 SAS AF: 0.000342

Gnomad4 FIN AF: 0.000869

Gnomad4 NFE AF: 0.000647

Gnomad4 OTH AF: 0.00593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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: rs1553563950; hg19: chr2-166150550;