2-165294010-TA-T

Position:

• chr2-165294010-TA-T

Variant summary

Our verdict is Benign. Variant got -9 ACMG points: 0P and 9B. BP6 BA1

The ENST00000283256(SCN2A):​c.-149delA variant causes a 5 prime UTR 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 ENST00000283256 5_prime_UTR
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 B:1
• Conservation: PhyloP100: 0.292

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 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -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/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-1735delA		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-1735delA		intron_variant		ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000283256	c.-149delA		5_prime_UTR_variant	1/27	1		ENSP00000283256.6
SCN2A	ENST00000375437.7	c.-51-1735delA		intron_variant		5	NM_001040142.2	ENSP00000364586.2
SCN2A	ENST00000631182.3	c.-51-1735delA		intron_variant		5	NM_001371246.1	ENSP00000486885.1
SCN2A	ENST00000424833.5	c.-51-1735delA		intron_variant		1		ENSP00000406454.2
SCN2A	ENST00000283256.10	c.-176delA		upstream_gene_variant		1		ENSP00000283256.6

Frequencies

GnomAD3 genomes AF: 0.166 AC: 9194 AN: 55422 Hom.: 307 Cov.: 0

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.: 95 Cov.: 0 AF XY: 0.123 AC XY: 5578 AN XY: 45496

Gnomad4 AFR exome AF: 0.0996

Gnomad4 AMR exome AF: 0.133

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.0909

Gnomad4 SAS exome AF: 0.139

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.121

Gnomad4 OTH exome AF: 0.124

GnomAD4 genome AF: 0.166 AC: 9194 AN: 55432 Hom.: 307 Cov.: 0 AF XY: 0.164 AC XY: 3963 AN XY: 24128

Gnomad4 AFR AF: 0.0897

Gnomad4 AMR AF: 0.179

Gnomad4 ASJ AF: 0.256

Gnomad4 EAS AF: 0.103

Gnomad4 SAS AF: 0.206

Gnomad4 FIN AF: 0.0772

Gnomad4 NFE AF: 0.193

Gnomad4 OTH AF: 0.181

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Uncertain:2 Benign:1

Revision: criteria provided, conflicting classifications

Submissions by phenotype

Early Infantile Epileptic Encephalopathy, Autosomal Dominant Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Seizures, benign familial infantile, 3 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Sep 24, 2019

- -

Computational scores

Source: dbNSFP v4.3

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

LitVar

Other links and lift over

dbSNP: rs67417831; hg19: chr2-166150520;