2-165294040-A-AAAAT

Position:

• chr2-165294040-A-AAAAT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000283256.10(SCN2A):​c.-147_-146insAAAT 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 0.000087 (0 hom., cov: 11)
  • Exomes 𝑓: 0.0000057 (0 hom.)
• Consequence: SCN2A ENST00000283256.10 5_prime_UTR
• Clinical Significance: Uncertain significance criteria provided, single submitter U:2
• 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 Likely_benign. Variant got -4 ACMG points.

• BS2: High AC in GnomAd4 at 9 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-1733_-51-1732insAAAT		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-1733_-51-1732insAAAT		intron_variant		ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.-51-1733_-51-1732insAAAT		intron_variant		5	NM_001040142.2	ENSP00000364586	P1
SCN2A	ENST00000631182.3	c.-51-1733_-51-1732insAAAT		intron_variant		5	NM_001371246.1	ENSP00000486885

Frequencies

GnomAD3 genomes AF: 0.0000868 AC: 9 AN: 103632 Hom.: 0 Cov.: 11

Gnomad AFR AF: 0.000108

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000302

Gnomad SAS AF: 0.000341

Gnomad FIN AF: 0.000289

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000571

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000570 AC: 3 AN: 526710 Hom.: 0 Cov.: 0 AF XY: 0.00000817 AC XY: 2 AN XY: 244876

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000622

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome AF: 0.0000868 AC: 9 AN: 103668 Hom.: 0 Cov.: 11 AF XY: 0.000104 AC XY: 5 AN XY: 47918

Gnomad4 AFR AF: 0.000108

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000302

Gnomad4 SAS AF: 0.000342

Gnomad4 FIN AF: 0.000289

Gnomad4 NFE AF: 0.0000571

Gnomad4 OTH AF: 0.00

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

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs780674346; hg19: chr2-166150550;