chr2-165294040-A-AT

Position:

• chr2-165294040-A-AT

Variant summary

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

The ENST00000283256.10(SCN2A):​c.-134dup variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.026 (98 hom., cov: 11)
  • Exomes 𝑓: 0.048 (38 hom.)
• Consequence: SCN2A ENST00000283256.10 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• 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: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.095 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-1720dup		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-1720dup		intron_variant		ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.-51-1720dup		intron_variant		5	NM_001040142.2	ENSP00000364586	P1
SCN2A	ENST00000631182.3	c.-51-1720dup		intron_variant		5	NM_001371246.1	ENSP00000486885

Frequencies

GnomAD3 genomes AF: 0.0260 AC: 2696 AN: 103626 Hom.: 99 Cov.: 11

Gnomad AFR AF: 0.0663

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0177

Gnomad ASJ AF: 0.0171

Gnomad EAS AF: 0.104

Gnomad SAS AF: 0.0358

Gnomad FIN AF: 0.00693

Gnomad MID AF: 0.00526

Gnomad NFE AF: 0.00302

Gnomad OTH AF: 0.0208

GnomAD4 exome AF: 0.0482 AC: 24503 AN: 508322 Hom.: 38 Cov.: 0 AF XY: 0.0482 AC XY: 11376 AN XY: 236238

Gnomad4 AFR exome AF: 0.113

Gnomad4 AMR exome AF: 0.0796

Gnomad4 ASJ exome AF: 0.0534

Gnomad4 EAS exome AF: 0.147

Gnomad4 SAS exome AF: 0.0908

Gnomad4 FIN exome AF: 0.0465

Gnomad4 NFE exome AF: 0.0450

Gnomad4 OTH exome AF: 0.0576

GnomAD4 genome AF: 0.0260 AC: 2695 AN: 103662 Hom.: 98 Cov.: 11 AF XY: 0.0282 AC XY: 1352 AN XY: 47910

Gnomad4 AFR AF: 0.0662

Gnomad4 AMR AF: 0.0177

Gnomad4 ASJ AF: 0.0171

Gnomad4 EAS AF: 0.104

Gnomad4 SAS AF: 0.0355

Gnomad4 FIN AF: 0.00693

Gnomad4 NFE AF: 0.00303

Gnomad4 OTH AF: 0.0208

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Early Infantile Epileptic Encephalopathy, Autosomal Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Seizures, benign familial infantile, 3 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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;