rs10184275

Variant names:

• chr2-165271418-G-A
• rs10184275
• NM_001040142.2:c.-51-24355G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-165271418-G-A
• chr2-165271418-G-C
• chr2-165271418-G-T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001040142.2(SCN2A):​c.-51-24355G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.857 in 152,044 control chromosomes in the GnomAD database, including 56,229 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.86 (56224 hom., cov: 31)
  • Exomes 𝑓: 0.78 (5 hom.)
• Consequence: SCN2A NM_001040142.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0770
• Publications: 9 publications found

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 Gene-Disease associations (from GenCC):

• complex neurodevelopmental disorder

  Inheritance: AD Classification: DEFINITIVE Submitted by: ClinGen, Illumina
• developmental and epileptic encephalopathy, 11

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• intellectual disability

  Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
• episodic ataxia, type 9

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae)
• seizures, benign familial infantile, 3

  Inheritance: AD Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics
• benign familial infantile epilepsy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• benign familial neonatal-infantile seizures

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• Dravet syndrome

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• genetic developmental and epileptic encephalopathy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• infantile spasms

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• malignant migrating partial seizures of infancy

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-1.0).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.953 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2A	NM_001040142.2	c.-51-24355G>A		intron_variant	Intron 1 of 26	ENST00000375437.7	NP_001035232.1
SCN2A	NM_001371246.1	c.-51-24355G>A		intron_variant	Intron 1 of 26	ENST00000631182.3	NP_001358175.1
SCN2A	NM_001040143.2	c.-51-24355G>A		intron_variant	Intron 2 of 27		NP_001035233.1
SCN2A	NM_001371247.1	c.-51-24355G>A		intron_variant	Intron 1 of 26		NP_001358176.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN2A	ENST00000375437.7	c.-51-24355G>A		intron_variant	Intron 1 of 26	5	NM_001040142.2	ENSP00000364586.2
SCN2A	ENST00000631182.3	c.-51-24355G>A		intron_variant	Intron 1 of 26	5	NM_001371246.1	ENSP00000486885.1
SCN2A	ENST00000424833.5	c.-51-24355G>A		intron_variant	Intron 1 of 10	1		ENSP00000406454.2

Frequencies

GnomAD3 genomes AF: 0.857 AC: 130142 AN: 151908 Hom.: 56169 Cov.: 31

Gnomad AFR AF: 0.961

Gnomad AMI AF: 0.683

Gnomad AMR AF: 0.847

Gnomad ASJ AF: 0.877

Gnomad EAS AF: 0.770

Gnomad SAS AF: 0.820

Gnomad FIN AF: 0.793

Gnomad MID AF: 0.924

Gnomad NFE AF: 0.815

Gnomad OTH AF: 0.862

GnomAD4 exome AF: 0.778 AC: 14 AN: 18 Hom.: 5 Cov.: 0 AF XY: 0.813 AC XY: 13 AN XY: 16

African (AFR) AC: 0 AN: 0

American (AMR) AC: 0 AN: 0

Ashkenazi Jewish (ASJ) AC: 0 AN: 0

East Asian (EAS) AF: 0.500 AC: 1 AN: 2

South Asian (SAS) AC: 0 AN: 0

European-Finnish (FIN) AF: 0.500 AC: 1 AN: 2

Middle Eastern (MID) AC: 0 AN: 0

European-Non Finnish (NFE) AF: 0.857 AC: 12 AN: 14

Other (OTH) AC: 0 AN: 0

GnomAD4 genome AF: 0.857 AC: 130252 AN: 152026 Hom.: 56224 Cov.: 31 AF XY: 0.855 AC XY: 63528 AN XY: 74318

African (AFR) AF: 0.961 AC: 39897 AN: 41520

American (AMR) AF: 0.846 AC: 12900 AN: 15242

Ashkenazi Jewish (ASJ) AF: 0.877 AC: 3042 AN: 3470

East Asian (EAS) AF: 0.770 AC: 3955 AN: 5136

South Asian (SAS) AF: 0.819 AC: 3946 AN: 4820

European-Finnish (FIN) AF: 0.793 AC: 8393 AN: 10578

Middle Eastern (MID) AF: 0.925 AC: 272 AN: 294

European-Non Finnish (NFE) AF: 0.815 AC: 55407 AN: 67946

Other (OTH) AF: 0.862 AC: 1817 AN: 2108

Alfa AF: 0.831 Hom.: 27922

Bravo AF: 0.867

Asia WGS AF: 0.822 AC: 2859 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-1.0
CADD	Benign	3.3
DANN	Benign	0.54
PhyloP100		0.077
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs10184275; hg19: chr2-166127928;