chr2-165294010-TA-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.-51-1735delA 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 0.17 ( 307 hom., cov: 0)

Exomes 𝑓: 0.12 ( 95 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: 0.292

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 -9 ACMG points.

BP6

Variant 2-165294010-TA-T is Benign according to our data. Variant chr2-165294010-TA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 331708.We mark this variant Likely_benign, oryginal submissions are: {Uncertain_significance=2, Benign=1}.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.189 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2A	NM_001040142.2 link	c.-51-1735delA		intron_variant	Intron 1 of 26	ENST00000375437.7	NP_001035232.1	Q99250-1
SCN2A	NM_001371246.1 link	c.-51-1735delA		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.-51-1762delA	intron_variant	Intron 1 of 26	5	NM_001040142.2	ENSP00000364586.2	Q99250-1
SCN2A	ENST00000631182.3 link	c.-51-1762delA	intron_variant	Intron 1 of 26	5	NM_001371246.1	ENSP00000486885.1	Q99250-2
SCN2A	ENST00000424833.5 link	c.-51-1762delA	intron_variant	Intron 1 of 10	1		ENSP00000406454.2	F6U291
SCN2A	ENST00000283256.10 link	c.-176delA	upstream_gene_variant		1		ENSP00000283256.6	Q99250-1

Frequencies

GnomAD3 genomes

AF:

0.166

AC:

9194

AN:

55422

Hom.:

307

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0897

Gnomad AMI

AF:

0.179

Gnomad AMR

AF:

0.180

Gnomad ASJ

AF:

0.256

Gnomad EAS

AF:

0.103

Gnomad SAS

AF:

0.206

Gnomad FIN

AF:

0.0772

Gnomad MID

AF:

0.188

Gnomad NFE

AF:

0.193

Gnomad OTH

AF:

0.181

GnomAD4 exome

AF:

0.121

AC:

11518

AN:

94806

Hom.:

Cov.:

AF XY:

0.123

AC XY:

5578

AN XY:

45496

show subpopulations

African (AFR)

AF:

0.0996

AC:

269

AN:

2700

American (AMR)

AF:

0.133

AC:

AN:

158

Ashkenazi Jewish (ASJ)

AF:

0.147

AC:

110

AN:

748

East Asian (EAS)

AF:

0.0909

AC:

AN:

440

South Asian (SAS)

AF:

0.139

AC:

300

AN:

2154

European-Finnish (FIN)

AF:

0.0714

AC:

AN:

Middle Eastern (MID)

AF:

0.148

AC:

AN:

236

European-Non Finnish (NFE)

AF:

0.121

AC:

10318

AN:

84930

Other (OTH)

AF:

0.124

AC:

422

AN:

3398

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

450

901

1351

1802

2252

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.166

AC:

9194

AN:

55432

Hom.:

307

Cov.:

AF XY:

0.164

AC XY:

3963

AN XY:

24128

show subpopulations

African (AFR)

AF:

0.0897

AC:

1217

AN:

13566

American (AMR)

AF:

0.179

AC:

598

AN:

3332

Ashkenazi Jewish (ASJ)

AF:

0.256

AC:

501

AN:

1958

East Asian (EAS)

AF:

0.103

AC:

154

AN:

1502

South Asian (SAS)

AF:

0.206

AC:

178

AN:

862

European-Finnish (FIN)

AF:

0.0772

AC:

AN:

298

Middle Eastern (MID)

AF:

0.196

AC:

AN:

European-Non Finnish (NFE)

AF:

0.193

AC:

6312

AN:

32746

Other (OTH)

AF:

0.181

AC:

113

AN:

624

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.412

Heterozygous variant carriers

293

586

878

1171

1464

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

Sep 24, 2019

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

(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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chr2-165294010-TA-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