2-165294010-TAAA-T

Position:

• chr2-165294010-TAAA-T

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BA1

The NM_001040142.2(SCN2A):​c.-51-1737_-51-1735del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0484 in 150,412 control chromosomes in the GnomAD database, including 24 homozygotes. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0076 (1 hom., cov: 0)
  • Exomes 𝑓: 0.073 (23 hom.)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.311

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 2-165294010-TAAA-T is Benign according to our data. Variant chr2-165294010-TAAA-T is described in ClinVar as [Likely_benign]. Clinvar id is 1703351.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAdExome4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.112 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-1737_-51-1735del		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-1737_-51-1735del		intron_variant		ENST00000631182.3	NP_001358175.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.-51-1737_-51-1735del		intron_variant		5	NM_001040142.2	ENSP00000364586	P1
SCN2A	ENST00000631182.3	c.-51-1737_-51-1735del		intron_variant		5	NM_001371246.1	ENSP00000486885

Frequencies

GnomAD3 genomes AF: 0.00760 AC: 425 AN: 55896 Hom.: 1 Cov.: 0

Gnomad AFR AF: 0.0109

Gnomad AMI AF: 0.00198

Gnomad AMR AF: 0.00328

Gnomad ASJ AF: 0.000505

Gnomad EAS AF: 0.0139

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00671

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00722

Gnomad OTH AF: 0.00315

GnomAD4 exome AF: 0.0726 AC: 6860 AN: 94506 Hom.: 23 AF XY: 0.0723 AC XY: 3278 AN XY: 45370

Gnomad4 AFR exome AF: 0.123

Gnomad4 AMR exome AF: 0.0577

Gnomad4 ASJ exome AF: 0.0921

Gnomad4 EAS exome AF: 0.0543

Gnomad4 SAS exome AF: 0.0527

Gnomad4 FIN exome AF: 0.0714

Gnomad4 NFE exome AF: 0.0714

Gnomad4 OTH exome AF: 0.0726

GnomAD4 genome AF: 0.00760 AC: 425 AN: 55906 Hom.: 1 Cov.: 0 AF XY: 0.00748 AC XY: 182 AN XY: 24326

Gnomad4 AFR AF: 0.0109

Gnomad4 AMR AF: 0.00327

Gnomad4 ASJ AF: 0.000505

Gnomad4 EAS AF: 0.0139

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00671

Gnomad4 NFE AF: 0.00722

Gnomad4 OTH AF: 0.00315

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

GeneDx

Feb 24, 2022

See Variant Classification Assertion Criteria. -

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;