2-165294040-A-AAAT

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The ENST00000283256(SCN2A):​c.-147_-146insAAT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000077 ( 0 hom., cov: 11)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

SCN2A
ENST00000283256 5_prime_UTR

Scores

Not classified

Clinical Significance

Uncertain significance criteria provided, single submitter U:2

Conservation

PhyloP100: 0.275
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2
High AC in GnomAd4 at 8 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
SCN2ANM_001040142.2 linkuse as main transcriptc.-51-1733_-51-1732insAAT intron_variant ENST00000375437.7 NP_001035232.1 Q99250-1
SCN2ANM_001371246.1 linkuse as main transcriptc.-51-1733_-51-1732insAAT intron_variant ENST00000631182.3 NP_001358175.1

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
SCN2AENST00000283256 linkuse as main transcriptc.-147_-146insAAT 5_prime_UTR_variant 1/271 ENSP00000283256.6 Q99250-1
SCN2AENST00000375437.7 linkuse as main transcriptc.-51-1733_-51-1732insAAT intron_variant 5 NM_001040142.2 ENSP00000364586.2 Q99250-1
SCN2AENST00000631182.3 linkuse as main transcriptc.-51-1733_-51-1732insAAT intron_variant 5 NM_001371246.1 ENSP00000486885.1 Q99250-2
SCN2AENST00000424833.5 linkuse as main transcriptc.-51-1733_-51-1732insAAT intron_variant 1 ENSP00000406454.2 F6U291

Frequencies

GnomAD3 genomes
AF:
0.0000772
AC:
8
AN:
103632
Hom.:
0
Cov.:
11
show subpopulations
Gnomad AFR
AF:
0.0000723
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.000380
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000341
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000761
Gnomad OTH
AF:
0.00
GnomAD4 exome
AF:
0.0000247
AC:
13
AN:
526648
Hom.:
0
Cov.:
0
AF XY:
0.0000286
AC XY:
7
AN XY:
244858
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000270
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
AF:
0.0000772
AC:
8
AN:
103668
Hom.:
0
Cov.:
11
AF XY:
0.000104
AC XY:
5
AN XY:
47914
show subpopulations
Gnomad4 AFR
AF:
0.0000722
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.000380
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000342
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000761
Gnomad4 OTH
AF:
0.00

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:2
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

Early Infantile Epileptic Encephalopathy, Autosomal Dominant Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -
Seizures, benign familial infantile, 3 Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingIllumina Laboratory Services, IlluminaJun 14, 2016- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs780674346; hg19: chr2-166150550; API