chr2-165294010-TAA-T

Position:

• chr2-165294010-TAA-T

Variant summary

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

The NM_001040142.2(SCN2A):​c.-51-1736_-51-1735del variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.135 in 149,934 control chromosomes in the GnomAD database, including 354 homozygotes. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

• Frequency:
  • Genomes: 𝑓 0.16 (283 hom., cov: 0)
  • Exomes 𝑓: 0.12 (71 hom.)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Conflicting classifications of pathogenicity criteria provided, conflicting classifications U:2 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 -9 ACMG points.

• BP6: Variant 2-165294010-TAA-T is Benign according to our data. Variant chr2-165294010-TAA-T is described in ClinVar as [Conflicting_classifications_of_pathogenicity]. Clinvar id is 331709.We mark this variant Likely_benign, oryginal submissions are: {Benign=1, Uncertain_significance=2}.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.283 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-1736_-51-1735del		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-1736_-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.-51-1736_-51-1735del		intron_variant		5	NM_001040142.2	ENSP00000364586	P1
SCN2A	ENST00000631182.3	c.-51-1736_-51-1735del		intron_variant		5	NM_001371246.1	ENSP00000486885

Frequencies

GnomAD3 genomes AF: 0.157 AC: 8707 AN: 55448 Hom.: 283 Cov.: 0

Gnomad AFR AF: 0.291

Gnomad AMI AF: 0.0556

Gnomad AMR AF: 0.129

Gnomad ASJ AF: 0.164

Gnomad EAS AF: 0.146

Gnomad SAS AF: 0.100

Gnomad FIN AF: 0.0980

Gnomad MID AF: 0.220

Gnomad NFE AF: 0.109

Gnomad OTH AF: 0.178

GnomAD4 exome AF: 0.121 AC: 11468 AN: 94476 Hom.: 71 AF XY: 0.122 AC XY: 5545 AN XY: 45344

Gnomad4 AFR exome AF: 0.180

Gnomad4 AMR exome AF: 0.0570

Gnomad4 ASJ exome AF: 0.180

Gnomad4 EAS exome AF: 0.133

Gnomad4 SAS exome AF: 0.110

Gnomad4 FIN exome AF: 0.0476

Gnomad4 NFE exome AF: 0.119

Gnomad4 OTH exome AF: 0.129

GnomAD4 genome AF: 0.157 AC: 8705 AN: 55458 Hom.: 283 Cov.: 0 AF XY: 0.163 AC XY: 3939 AN XY: 24158

Gnomad4 AFR AF: 0.290

Gnomad4 AMR AF: 0.129

Gnomad4 ASJ AF: 0.164

Gnomad4 EAS AF: 0.146

Gnomad4 SAS AF: 0.100

Gnomad4 FIN AF: 0.0980

Gnomad4 NFE AF: 0.109

Gnomad4 OTH AF: 0.178

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

Jan 20, 2021

- -

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;