ENST00000283256:c.-136_-134dupTTT

Variant names:

• chr2-165294040-A-ATTT
• rs1553563950
• ENST00000283256:c.-136_-134dupTTT

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The ENST00000283256(SCN2A):​c.-136_-134dupTTT variant causes a 5 prime UTR change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.00076 (1 hom., cov: 11)
  • Exomes 𝑓: 0.0053 (1 hom.)
• Consequence: SCN2A ENST00000283256 5_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.275

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]

ACMG classification

Verdict is Benign. Variant got -10 ACMG points.

• BP6: Variant 2-165294040-A-ATTT is Benign according to our data. Variant chr2-165294040-A-ATTT is described in ClinVar as [Benign]. Clinvar id is 2651482.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.000762 (79/103682) while in subpopulation NFE AF= 0.0012 (63/52558). AF 95% confidence interval is 0.000961. There are 1 homozygotes in gnomad4. There are 36 alleles in male gnomad4 subpopulation. Median coverage is 11. This position pass quality control queck.
• BS2: High AC in GnomAd4 at 79 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-1722_-51-1720dupTTT		intron_variant	Intron 1 of 26	ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-1722_-51-1720dupTTT		intron_variant	Intron 1 of 26	ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000283256	c.-136_-134dupTTT		5_prime_UTR_variant	Exon 1 of 27	1		ENSP00000283256.6
SCN2A	ENST00000375437.7	c.-51-1722_-51-1720dupTTT		intron_variant	Intron 1 of 26	5	NM_001040142.2	ENSP00000364586.2
SCN2A	ENST00000631182.3	c.-51-1722_-51-1720dupTTT		intron_variant	Intron 1 of 26	5	NM_001371246.1	ENSP00000486885.1
SCN2A	ENST00000424833.5	c.-51-1722_-51-1720dupTTT		intron_variant	Intron 1 of 10	1		ENSP00000406454.2

Frequencies

GnomAD3 genomes AF: 0.000762 AC: 79 AN: 103646 Hom.: 1 Cov.: 11

Gnomad AFR AF: 0.000289

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000341

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000905

Gnomad SAS AF: 0.000682

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00120

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00530 AC: 2784 AN: 525350 Hom.: 1 Cov.: 0 AF XY: 0.00530 AC XY: 1294 AN XY: 244284

Gnomad4 AFR exome AF: 0.00143

Gnomad4 AMR exome AF: 0.00457

Gnomad4 ASJ exome AF: 0.00260

Gnomad4 EAS exome AF: 0.00701

Gnomad4 SAS exome AF: 0.00405

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00541

Gnomad4 OTH exome AF: 0.00552

GnomAD4 genome AF: 0.000762 AC: 79 AN: 103682 Hom.: 1 Cov.: 11 AF XY: 0.000751 AC XY: 36 AN XY: 47926

Gnomad4 AFR AF: 0.000289

Gnomad4 AMR AF: 0.000340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000906

Gnomad4 SAS AF: 0.000683

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00120

Gnomad4 OTH AF: 0.00

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Sep 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

SCN2A: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs1553563950; hg19: chr2-166150550;