chr2-165294010-T-TAA

Variant names:

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BA1

The NM_001040142.2(SCN2A):c.-51-1736_-51-1735dupAA variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.31 ( 3463 hom., cov: 0)

Exomes 𝑓: 0.058 ( 51 hom. )

Consequence

SCN2A
NM_001040142.2 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:4B:1

Conservation

PhyloP100: 0.292

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 Submitted by: ClinGen, Illumina
developmental and epileptic encephalopathy, 11
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
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: Labcorp Genetics (formerly Invitae), Ambry Genetics
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: Benign. The variant received -8 ACMG points.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.369 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2A	NM_001040142.2 link	c.-51-1736_-51-1735dupAA		intron_variant	Intron 1 of 26	ENST00000375437.7	NP_001035232.1	Q99250-1
SCN2A	NM_001371246.1 link	c.-51-1736_-51-1735dupAA		intron_variant	Intron 1 of 26	ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN2A	ENST00000375437.7 link	c.-51-1763_-51-1762insAA	intron_variant	Intron 1 of 26	5	NM_001040142.2	ENSP00000364586.2	Q99250-1
SCN2A	ENST00000631182.3 link	c.-51-1763_-51-1762insAA	intron_variant	Intron 1 of 26	5	NM_001371246.1	ENSP00000486885.1	Q99250-2
SCN2A	ENST00000424833.5 link	c.-51-1763_-51-1762insAA	intron_variant	Intron 1 of 10	1		ENSP00000406454.2	F6U291
SCN2A	ENST00000283256.10 link	c.-177_-176insAA	upstream_gene_variant		1		ENSP00000283256.6	Q99250-1

Frequencies

GnomAD3 genomes

AF:

0.313

AC:

17586

AN:

56108

Hom.:

3463

Cov.:

show subpopulations

Gnomad AFR

AF:

0.179

Gnomad AMI

AF:

0.309

Gnomad AMR

AF:

0.304

Gnomad ASJ

AF:

0.248

Gnomad EAS

AF:

0.347

Gnomad SAS

AF:

0.269

Gnomad FIN

AF:

0.226

Gnomad MID

AF:

0.125

Gnomad NFE

AF:

0.374

Gnomad OTH

AF:

0.308

GnomAD4 exome

AF:

0.0580

AC:

5485

AN:

94626

Hom.:

Cov.:

AF XY:

0.0597

AC XY:

2710

AN XY:

45412

show subpopulations

African (AFR)

AF:

0.0219

AC:

AN:

2696

American (AMR)

AF:

0.0253

AC:

AN:

158

Ashkenazi Jewish (ASJ)

AF:

0.0161

AC:

AN:

746

East Asian (EAS)

AF:

0.0430

AC:

AN:

442

South Asian (SAS)

AF:

0.0438

AC:

AN:

2144

European-Finnish (FIN)

AF:

0.0952

AC:

AN:

Middle Eastern (MID)

AF:

0.0378

AC:

AN:

238

European-Non Finnish (NFE)

AF:

0.0604

AC:

5115

AN:

84744

Other (OTH)

AF:

0.0495

AC:

169

AN:

3416

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

209

419

628

838

1047

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.313

AC:

17586

AN:

56118

Hom.:

3463

Cov.:

AF XY:

0.300

AC XY:

7337

AN XY:

24424

show subpopulations

African (AFR)

AF:

0.179

AC:

2435

AN:

13634

American (AMR)

AF:

0.304

AC:

1020

AN:

3354

Ashkenazi Jewish (ASJ)

AF:

0.248

AC:

494

AN:

1992

East Asian (EAS)

AF:

0.347

AC:

526

AN:

1518

South Asian (SAS)

AF:

0.269

AC:

236

AN:

876

European-Finnish (FIN)

AF:

0.226

AC:

AN:

296

Middle Eastern (MID)

AF:

0.130

AC:

AN:

European-Non Finnish (NFE)

AF:

0.374

AC:

12450

AN:

33260

Other (OTH)

AF:

0.308

AC:

197

AN:

640

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.575

Heterozygous variant carriers

410

820

1230

1640

2050

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:4Benign:1

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Early Infantile Epileptic Encephalopathy, Autosomal Dominant

Uncertain:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

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:2

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Feb 21, 2020

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

0.29

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

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.

chr2-165294010-T-TAA

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over