chr2-165294040-A-ATT

Position:

• chr2-165294040-A-ATT

Variant summary

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

The ENST00000283256.10(SCN2A):​c.-135_-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 0.21 (2525 hom., cov: 11)
  • Exomes 𝑓: 0.23 (4158 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 = 0.325 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-1721_-51-1720dup		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-1721_-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.-51-1721_-51-1720dup		intron_variant		5	NM_001040142.2	ENSP00000364586	P1
SCN2A	ENST00000631182.3	c.-51-1721_-51-1720dup		intron_variant		5	NM_001371246.1	ENSP00000486885

Frequencies

GnomAD3 genomes AF: 0.209 AC: 21599 AN: 103568 Hom.: 2519 Cov.: 11

Gnomad AFR AF: 0.0898

Gnomad AMI AF: 0.361

Gnomad AMR AF: 0.261

Gnomad ASJ AF: 0.155

Gnomad EAS AF: 0.341

Gnomad SAS AF: 0.189

Gnomad FIN AF: 0.0988

Gnomad MID AF: 0.0691

Gnomad NFE AF: 0.263

Gnomad OTH AF: 0.217

GnomAD4 exome AF: 0.233 AC: 120560 AN: 516672 Hom.: 4158 Cov.: 0 AF XY: 0.234 AC XY: 56268 AN XY: 240180

Gnomad4 AFR exome AF: 0.0742

Gnomad4 AMR exome AF: 0.284

Gnomad4 ASJ exome AF: 0.148

Gnomad4 EAS exome AF: 0.290

Gnomad4 SAS exome AF: 0.202

Gnomad4 FIN exome AF: 0.311

Gnomad4 NFE exome AF: 0.238

Gnomad4 OTH exome AF: 0.218

GnomAD4 genome AF: 0.209 AC: 21614 AN: 103602 Hom.: 2525 Cov.: 11 AF XY: 0.198 AC XY: 9490 AN XY: 47888

Gnomad4 AFR AF: 0.0898

Gnomad4 AMR AF: 0.261

Gnomad4 ASJ AF: 0.155

Gnomad4 EAS AF: 0.342

Gnomad4 SAS AF: 0.189

Gnomad4 FIN AF: 0.0988

Gnomad4 NFE AF: 0.263

Gnomad4 OTH AF: 0.220

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

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;