chr2-165294039-G-A

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>A 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. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.022 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0076 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

SCN2A
ENST00000283256.10 5_prime_UTR

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

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=-0.87).

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>A	intron	N/A	NP_001035232.1	Q99250-1
SCN2A	NM_001371246.1	MANE Plus Clinical	c.-51-1734G>A	intron	N/A	NP_001358175.1	Q99250-2
SCN2A	NM_001040143.2		c.-51-1734G>A	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>A	5_prime_UTR	Exon 1 of 27	ENSP00000283256.6	Q99250-1
SCN2A	ENST00000375437.7	TSL:5 MANE Select	c.-51-1734G>A	intron	N/A	ENSP00000364586.2	Q99250-1
SCN2A	ENST00000631182.3	TSL:5 MANE Plus Clinical	c.-51-1734G>A	intron	N/A	ENSP00000486885.1	Q99250-2

Frequencies

GnomAD3 genomes

AF:

0.0222

AC:

1111

AN:

49938

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0153

Gnomad AMI

AF:

0.0248

Gnomad AMR

AF:

0.0208

Gnomad ASJ

AF:

0.0140

Gnomad EAS

AF:

0.0270

Gnomad SAS

AF:

0.0183

Gnomad FIN

AF:

0.0110

Gnomad MID

AF:

0.0192

Gnomad NFE

AF:

0.0288

Gnomad OTH

AF:

0.0269

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00758

AC:

1658

AN:

218744

Hom.:

Cov.:

AF XY:

0.00726

AC XY:

747

AN XY:

102842

show subpopulations

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

African (AFR)

AF:

0.00161

AC:

AN:

4964

American (AMR)

AF:

0.0140

AC:

AN:

286

Ashkenazi Jewish (ASJ)

AF:

0.00267

AC:

AN:

1498

East Asian (EAS)

AF:

0.00893

AC:

AN:

896

South Asian (SAS)

AF:

0.00570

AC:

AN:

4388

European-Finnish (FIN)

AF:

0.00

AC:

AN:

Middle Eastern (MID)

AF:

0.00431

AC:

AN:

464

European-Non Finnish (NFE)

AF:

0.00782

AC:

1557

AN:

199060

Other (OTH)

AF:

0.00701

AC:

AN:

7128

⚠️ 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: 0.265

Heterozygous variant carriers

183

366

549

732

915

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

184

276

368

460

<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:

0.0223

AC:

1113

AN:

49934

Hom.:

Cov.:

AF XY:

0.0234

AC XY:

548

AN XY:

23428

show subpopulations

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

African (AFR)

AF:

0.0153

AC:

251

AN:

16368

American (AMR)

AF:

0.0208

AC:

AN:

4140

Ashkenazi Jewish (ASJ)

AF:

0.0140

AC:

AN:

1502

East Asian (EAS)

AF:

0.0271

AC:

AN:

1218

South Asian (SAS)

AF:

0.0184

AC:

AN:

1466

European-Finnish (FIN)

AF:

0.0110

AC:

AN:

1630

Middle Eastern (MID)

AF:

0.0213

AC:

AN:

European-Non Finnish (NFE)

AF:

0.0288

AC:

649

AN:

22560

Other (OTH)

AF:

0.0282

AC:

AN:

674

⚠️ 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: 0.292

Heterozygous variant carriers

194

292

389

486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

100

<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

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Seizures, benign familial infantile, 3 (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.17

(source)

DANN

Benign

0.36

PhyloP100

-0.39

PromoterAI

-0.014

Neutral

(source)

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

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