2-165294037-AAG-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The ENST00000283256.10(SCN2A):c.-148_-147del 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 0.00033 (0 hom., cov: 0)
  • Exomes 𝑓: 0.000077 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCN2A ENST00000283256.10 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• Conservation: PhyloP100: -0.380

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN2A	NM_001040142.2	c.-51-1734_-51-1733del		intron_variant		ENST00000375437.7
SCN2A	NM_001371246.1	c.-51-1734_-51-1733del		intron_variant		ENST00000631182.3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN2A	ENST00000375437.7	c.-51-1734_-51-1733del		intron_variant		5	NM_001040142.2	P1
SCN2A	ENST00000631182.3	c.-51-1734_-51-1733del		intron_variant		5	NM_001371246.1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 42 AN: 131894 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000497

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000163

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000241

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000327

Gnomad OTH AF: 0.000561

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.0000766 AC: 56 AN: 731500 Hom.: 0 AF XY: 0.0000737 AC XY: 25 AN XY: 339186

Gnomad4 AFR exome AF: 0.0000736

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000322

Gnomad4 SAS exome AF: 0.000207

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000702

Gnomad4 OTH exome AF: 0.000168

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000326 AC: 43 AN: 131936 Hom.: 0 Cov.: 0 AF XY: 0.000377 AC XY: 24 AN XY: 63592

Gnomad4 AFR AF: 0.000496

Gnomad4 AMR AF: 0.000163

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000242

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000343

Gnomad4 OTH AF: 0.000558

Alfa AF: 0.000553 Hom.: 0

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

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

- -

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)		0.010		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: rs1553563943; hg19: chr2-166150547;