chr2-165294038-AG-A

Position:

• chr2-165294038-AG-A

Variant summary

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

The ENST00000283256.10(SCN2A):​c.-148del 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 0.00074 (0 hom., cov: 0)
  • Exomes 𝑓: 0.00024 (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: -0.385

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	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-1734del		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-1734del		intron_variant		ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.-51-1734del		intron_variant		5	NM_001040142.2	ENSP00000364586	P1
SCN2A	ENST00000631182.3	c.-51-1734del		intron_variant		5	NM_001371246.1	ENSP00000486885

Frequencies

GnomAD3 genomes AF: 0.00 AC: 90 AN: 122232 Hom.: 0 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.000469

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000447

Gnomad ASJ AF: 0.00239

Gnomad EAS AF: 0.000835

Gnomad SAS AF: 0.00219

Gnomad FIN AF: 0.000142

Gnomad MID AF: 0.00769

Gnomad NFE AF: 0.000824

Gnomad OTH AF: 0.000625

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.000236 AC: 160 AN: 677174 Hom.: 0 Cov.: 0 AF XY: 0.000219 AC XY: 69 AN XY: 314528

Gnomad4 AFR exome AF: 0.000403

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.000250

Gnomad4 EAS exome AF: 0.000687

Gnomad4 SAS exome AF: 0.000228

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.000232

Gnomad4 OTH exome AF: 0.000227

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.000744 AC: 91 AN: 122274 Hom.: 0 Cov.: 0 AF XY: 0.000888 AC XY: 52 AN XY: 58578

Gnomad4 AFR AF: 0.000497

Gnomad4 AMR AF: 0.000447

Gnomad4 ASJ AF: 0.00239

Gnomad4 EAS AF: 0.000838

Gnomad4 SAS AF: 0.00219

Gnomad4 FIN AF: 0.000142

Gnomad4 NFE AF: 0.000824

Gnomad4 OTH AF: 0.000622

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)		0.0		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: rs886054994; hg19: chr2-166150548;