2-165294010-TAAAAAAAAAA-T

Variant summary

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

The NM_001040142.2(SCN2A):​c.-51-1744_-51-1735delAAAAAAAAAA variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.0050 ( 8 hom., cov: 0)
Exomes 𝑓: 0.00090 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

SCN2A
NM_001040142.2 intron

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.78

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

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 (AMR) allele frequency at 95% confidence interval = 0.0511 is higher than 0.05.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
SCN2ANM_001040142.2 linkc.-51-1744_-51-1735delAAAAAAAAAA intron_variant Intron 1 of 26 ENST00000375437.7 NP_001035232.1 Q99250-1
SCN2ANM_001371246.1 linkc.-51-1744_-51-1735delAAAAAAAAAA intron_variant Intron 1 of 26 ENST00000631182.3 NP_001358175.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
SCN2AENST00000375437.7 linkc.-51-1762_-51-1753delAAAAAAAAAA intron_variant Intron 1 of 26 5 NM_001040142.2 ENSP00000364586.2 Q99250-1
SCN2AENST00000631182.3 linkc.-51-1762_-51-1753delAAAAAAAAAA intron_variant Intron 1 of 26 5 NM_001371246.1 ENSP00000486885.1 Q99250-2
SCN2AENST00000424833.5 linkc.-51-1762_-51-1753delAAAAAAAAAA intron_variant Intron 1 of 10 1 ENSP00000406454.2 F6U291
SCN2AENST00000283256.10 linkc.-176_-167delAAAAAAAAAA upstream_gene_variant 1 ENSP00000283256.6 Q99250-1

Frequencies

GnomAD3 genomes
AF:
0.00501
AC:
280
AN:
55932
Hom.:
8
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00228
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.0578
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.0219
Gnomad SAS
AF:
0.00231
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.0208
Gnomad NFE
AF:
0.000272
Gnomad OTH
AF:
0.0142
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.000904
AC:
86
AN:
95122
Hom.:
0
AF XY:
0.000635
AC XY:
29
AN XY:
45646
show subpopulations
African (AFR)
AF:
0.000739
AC:
2
AN:
2706
American (AMR)
AF:
0.125
AC:
20
AN:
160
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
748
East Asian (EAS)
AF:
0.0338
AC:
15
AN:
444
South Asian (SAS)
AF:
0.000927
AC:
2
AN:
2158
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
42
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
238
European-Non Finnish (NFE)
AF:
0.000258
AC:
22
AN:
85206
Other (OTH)
AF:
0.00731
AC:
25
AN:
3420
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.531
Heterozygous variant carriers
0
3
6
9
12
15
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
10
20
30
40
50
<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
AF:
0.00501
AC:
280
AN:
55942
Hom.:
8
Cov.:
0
AF XY:
0.00579
AC XY:
141
AN XY:
24338
show subpopulations
African (AFR)
AF:
0.00228
AC:
31
AN:
13604
American (AMR)
AF:
0.0577
AC:
195
AN:
3380
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
1982
East Asian (EAS)
AF:
0.0219
AC:
33
AN:
1508
South Asian (SAS)
AF:
0.00231
AC:
2
AN:
864
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
298
Middle Eastern (MID)
AF:
0.0217
AC:
1
AN:
46
European-Non Finnish (NFE)
AF:
0.000272
AC:
9
AN:
33120
Other (OTH)
AF:
0.0142
AC:
9
AN:
636
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.568
Heterozygous variant carriers
0
10
19
29
38
48
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Genome Het
Genome Hom
Variant carriers
0
10
20
30
40
50
<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.:
0

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.8
Mutation Taster
=99/1
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs67417831; hg19: chr2-166150520; API