Genetic Variant SCN2A:c.-147_-146insAATTT (chr2-165294040-A-AAATTT) – ACMG Classification: Likely_benign (-4 pts)

Variant summary

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

The ENST00000283256(SCN2A):c.-147_-146insAATTT 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 0.000077 ( 0 hom., cov: 11)

Exomes 𝑓: 0.0000057 ( 0 hom. )

Consequence

SCN2A
ENST00000283256 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.275

Variant links:

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]

SCN2A links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2A	NM_001040142.2 link	c.-51-1733_-51-1732insAATTT		intron_variant	Intron 1 of 26	ENST00000375437.7	NP_001035232.1	Q99250-1
SCN2A	NM_001371246.1 link	c.-51-1733_-51-1732insAATTT		intron_variant	Intron 1 of 26	ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN2A	ENST00000283256 link	c.-147_-146insAATTT	5_prime_UTR_variant	Exon 1 of 27	1		ENSP00000283256.6	Q99250-1
SCN2A	ENST00000375437.7 link	c.-51-1733_-51-1732insAATTT	intron_variant	Intron 1 of 26	5	NM_001040142.2	ENSP00000364586.2	Q99250-1
SCN2A	ENST00000631182.3 link	c.-51-1733_-51-1732insAATTT	intron_variant	Intron 1 of 26	5	NM_001371246.1	ENSP00000486885.1	Q99250-2
SCN2A	ENST00000424833.5 link	c.-51-1733_-51-1732insAATTT	intron_variant	Intron 1 of 10	1		ENSP00000406454.2	F6U291

Frequencies

GnomAD3 genomes

AF:

0.0000772

AC:

AN:

103642

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000361

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000227

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000761

Gnomad OTH

AF:

0.000743

GnomAD4 exome

AF:

0.00000570

AC:

AN:

526700

Hom.:

Cov.:

AF XY:

0.00000817

AC XY:

AN XY:

244878

show subpopulations

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:

0.0000772

AC:

AN:

103678

Hom.:

Cov.:

AF XY:

0.0000835

AC XY:

AN XY:

47922

show subpopulations

Gnomad4 AFR

AF:

0.0000361

Gnomad4 AMR

AF:

0.000227

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000761

Gnomad4 OTH

AF:

0.000741

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:2

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Early Infantile Epileptic Encephalopathy, Autosomal Dominant

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Seizures, benign familial infantile, 3

Uncertain:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over