2-165294039-G-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The ENST00000283256.10(SCN2A):c.-148G>T variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.00033 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0030 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCN2A
ENST00000283256.10 5_prime_UTR

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.385

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

complex neurodevelopmental disorder
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Illumina, ClinGen, PanelApp Australia
developmental and epileptic encephalopathy, 11
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
intellectual disability
Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
episodic ataxia, type 9
Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
seizures, benign familial infantile, 3
Inheritance: AD Classification: STRONG Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
benign familial infantile epilepsy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
benign familial neonatal-infantile seizures
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Dravet syndrome
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
genetic developmental and epileptic encephalopathy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
infantile spasms
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
malignant migrating partial seizures of infancy
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

SCN2A links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.89).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000283256.10. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN2A	NM_001040142.2	MANE Select	c.-51-1734G>T	intron	N/A	NP_001035232.1	Q99250-1
SCN2A	NM_001371246.1	MANE Plus Clinical	c.-51-1734G>T	intron	N/A	NP_001358175.1	Q99250-2
SCN2A	NM_001040143.2		c.-51-1734G>T	intron	N/A	NP_001035233.1	Q99250-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
SCN2A	ENST00000283256.10	TSL:1	c.-148G>T	5_prime_UTR	Exon 1 of 27	ENSP00000283256.6	Q99250-1
SCN2A	ENST00000375437.7	TSL:5 MANE Select	c.-51-1734G>T	intron	N/A	ENSP00000364586.2	Q99250-1
SCN2A	ENST00000631182.3	TSL:5 MANE Plus Clinical	c.-51-1734G>T	intron	N/A	ENSP00000486885.1	Q99250-2

Frequencies

GnomAD3 genomes

AF:

0.000330

AC:

AN:

51562

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000359

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000789

Gnomad SAS

AF:

0.000660

Gnomad FIN

AF:

0.00182

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000254

Gnomad OTH

AF:

0.00

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00300

AC:

658

AN:

219340

Hom.:

Cov.:

AF XY:

0.00293

AC XY:

302

AN XY:

103040

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00612

AC:

AN:

4898

American (AMR)

AF:

0.00

AC:

AN:

288

Ashkenazi Jewish (ASJ)

AF:

0.00409

AC:

AN:

1468

East Asian (EAS)

AF:

0.00336

AC:

AN:

894

South Asian (SAS)

AF:

0.00320

AC:

AN:

4378

European-Finnish (FIN)

AF:

0.0161

AC:

AN:

Middle Eastern (MID)

AF:

0.00433

AC:

AN:

462

European-Non Finnish (NFE)

AF:

0.00291

AC:

582

AN:

199752

Other (OTH)

AF:

0.00280

AC:

AN:

7138

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.257

Heterozygous variant carriers

168

251

335

419

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

128

160

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000330

AC:

AN:

51558

Hom.:

Cov.:

AF XY:

0.000331

AC XY:

AN XY:

24134

show subpopulations

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.000359

AC:

AN:

16722

American (AMR)

AF:

0.00

AC:

AN:

4224

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

1546

East Asian (EAS)

AF:

0.000792

AC:

AN:

1262

South Asian (SAS)

AF:

0.000663

AC:

AN:

1508

European-Finnish (FIN)

AF:

0.00182

AC:

AN:

1650

Middle Eastern (MID)

AF:

0.00

AC:

AN:

European-Non Finnish (NFE)

AF:

0.000255

AC:

AN:

23574

Other (OTH)

AF:

0.00

AC:

AN:

684

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 0.5. (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.287

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.00

Hom.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.89

CADD

Benign

0.21

(source)

DANN

Benign

0.31

PhyloP100

-0.39

PromoterAI

-0.0013

Neutral

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over