chr2-165294010-T-TAAA

Position:

• chr2-165294010-T-TAAA

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BA1

The NM_001040142.2(SCN2A):​c.-51-1737_-51-1735dup variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Uncertain significance (★★).

• Frequency:
  • Genomes: 𝑓 0.070 (395 hom., cov: 0)
  • Exomes 𝑓: 0.058 (50 hom.)
  • Failed GnomAD Quality Control
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Uncertain significance criteria provided, multiple submitters, no conflicts U:3
• 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]

ACMG classification

Verdict is Benign. Variant got -8 ACMG points.

• BA1: GnomAdExome4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0591 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-1737_-51-1735dup		intron_variant		ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-1737_-51-1735dup		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_-51-1735dup		intron_variant		5	NM_001040142.2	ENSP00000364586	P1
SCN2A	ENST00000631182.3	c.-51-1737_-51-1735dup		intron_variant		5	NM_001371246.1	ENSP00000486885

Frequencies

GnomAD3 genomes AF: 0.0699 AC: 3908 AN: 55916 Hom.: 395 Cov.: 0

Gnomad AFR AF: 0.0466

Gnomad AMI AF: 0.141

Gnomad AMR AF: 0.0387

Gnomad ASJ AF: 0.0374

Gnomad EAS AF: 0.00862

Gnomad SAS AF: 0.0219

Gnomad FIN AF: 0.105

Gnomad MID AF: 0.0833

Gnomad NFE AF: 0.0874

Gnomad OTH AF: 0.0584

GnomAD4 exome AF: 0.0576 AC: 5443 AN: 94492 Hom.: 50 Cov.: 0 AF XY: 0.0575 AC XY: 2607 AN XY: 45348

Gnomad4 AFR exome AF: 0.0181

Gnomad4 AMR exome AF: 0.0313

Gnomad4 ASJ exome AF: 0.0227

Gnomad4 EAS exome AF: 0.0315

Gnomad4 SAS exome AF: 0.0276

Gnomad4 FIN exome AF: 0.119

Gnomad4 NFE exome AF: 0.0605

Gnomad4 OTH exome AF: 0.0500

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0699 AC: 3908 AN: 55926 Hom.: 395 Cov.: 0 AF XY: 0.0680 AC XY: 1656 AN XY: 24340

Gnomad4 AFR AF: 0.0466

Gnomad4 AMR AF: 0.0386

Gnomad4 ASJ AF: 0.0374

Gnomad4 EAS AF: 0.00862

Gnomad4 SAS AF: 0.0219

Gnomad4 FIN AF: 0.105

Gnomad4 NFE AF: 0.0874

Gnomad4 OTH AF: 0.0584

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:3

Revision: criteria provided, multiple submitters, no conflicts

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

- -

not provided Uncertain:1

Uncertain significance, criteria provided, single submitter

not provided

Breakthrough Genomics, Breakthrough Genomics

-

- -

Seizures, benign familial infantile, 3 Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs67417831; hg19: chr2-166150520;