2-165294010-TAA-T

Variant names:

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP6BA1

The NM_001040142.2(SCN2A):c.-51-1736_-51-1735delAA variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 149,934 control chromosomes in the GnomAD database, including 354 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.16 ( 283 hom., cov: 0)

Exomes 𝑓: 0.12 ( 71 hom. )

Consequence

SCN2A
NM_001040142.2 intron

Scores

Not classified

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2B:1

Conservation

PhyloP100: 0.311

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 -9 ACMG points.

BP6

Variant 2-165294010-TAA-T is Benign according to our data. Variant chr2-165294010-TAA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 331709.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 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_-51-1735delAA		intron_variant	Intron 1 of 26	ENST00000375437.7	NP_001035232.1	Q99250-1
SCN2A	NM_001371246.1 link	c.-51-1736_-51-1735delAA		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.-51-1762_-51-1761delAA	intron_variant	Intron 1 of 26	5	NM_001040142.2	ENSP00000364586.2	Q99250-1
SCN2A	ENST00000631182.3 link	c.-51-1762_-51-1761delAA	intron_variant	Intron 1 of 26	5	NM_001371246.1	ENSP00000486885.1	Q99250-2
SCN2A	ENST00000424833.5 link	c.-51-1762_-51-1761delAA	intron_variant	Intron 1 of 10	1		ENSP00000406454.2	F6U291
SCN2A	ENST00000283256.10 link	c.-176_-175delAA	upstream_gene_variant		1		ENSP00000283256.6	Q99250-1

Frequencies

GnomAD3 genomes

AF:

0.157

AC:

8707

AN:

55448

Hom.:

283

Cov.:

show subpopulations

Gnomad AFR

AF:

0.291

Gnomad AMI

AF:

0.0556

Gnomad AMR

AF:

0.129

Gnomad ASJ

AF:

0.164

Gnomad EAS

AF:

0.146

Gnomad SAS

AF:

0.100

Gnomad FIN

AF:

0.0980

Gnomad MID

AF:

0.220

Gnomad NFE

AF:

0.109

Gnomad OTH

AF:

0.178

GnomAD4 exome

AF:

0.121

AC:

11468

AN:

94476

Hom.:

AF XY:

0.122

AC XY:

5545

AN XY:

45344

show subpopulations

African (AFR)

AF:

0.180

AC:

484

AN:

2690

American (AMR)

AF:

0.0570

AC:

AN:

158

Ashkenazi Jewish (ASJ)

AF:

0.180

AC:

134

AN:

746

East Asian (EAS)

AF:

0.133

AC:

AN:

442

South Asian (SAS)

AF:

0.110

AC:

237

AN:

2146

European-Finnish (FIN)

AF:

0.0476

AC:

AN:

Middle Eastern (MID)

AF:

0.184

AC:

AN:

234

European-Non Finnish (NFE)

AF:

0.119

AC:

10060

AN:

84618

Other (OTH)

AF:

0.129

AC:

440

AN:

3400

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.439

Heterozygous variant carriers

402

804

1206

1608

2010

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.157

AC:

8705

AN:

55458

Hom.:

283

Cov.:

AF XY:

0.163

AC XY:

3939

AN XY:

24158

show subpopulations

African (AFR)

AF:

0.290

AC:

3889

AN:

13388

American (AMR)

AF:

0.129

AC:

430

AN:

3346

Ashkenazi Jewish (ASJ)

AF:

0.164

AC:

325

AN:

1980

East Asian (EAS)

AF:

0.146

AC:

220

AN:

1502

South Asian (SAS)

AF:

0.100

AC:

AN:

858

European-Finnish (FIN)

AF:

0.0980

AC:

AN:

296

Middle Eastern (MID)

AF:

0.208

AC:

AN:

European-Non Finnish (NFE)

AF:

0.109

AC:

3575

AN:

32900

Other (OTH)

AF:

0.178

AC:

113

AN:

636

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.421

Heterozygous variant carriers

268

537

805

1074

1342

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:2Benign:1

Revision: criteria provided, conflicting classifications

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

- -

not provided

Benign:1

Jan 20, 2021

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

0.31

Mutation Taster

=100/0

polymorphism

(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

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2-165294010-TAA-T

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