rs2217199

Variant names:

• chr2-166053185-A-C
• rs2217199
• NM_001165963.4:c.603-242T>G

Your query was ambiguous. Multiple possible variants found:

• chr2-166053185-A-C
• chr2-166053185-A-G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_001165963.4(SCN1A):​c.603-242T>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000164 in 609,756 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000016 (0 hom.)
• Consequence: SCN1A NM_001165963.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.116
• Publications: 0 publications found

Genes affected

SCN1A (HGNC:10585): (sodium voltage-gated channel alpha subunit 1) Voltage-dependent sodium channels are heteromeric complexes that regulate sodium exchange between intracellular and extracellular spaces and are essential for the generation and propagation of action potentials in muscle cells and neurons. Each sodium channel is composed of a large pore-forming, glycosylated alpha subunit and two smaller beta subunits. This gene encodes a sodium channel alpha subunit, which has four homologous domains, each of which contains six transmembrane regions. Allelic variants of this gene are associated with generalized epilepsy with febrile seizures and epileptic encephalopathy. Alternative splicing results in multiple transcript variants. The RefSeq Project has decided to create four representative RefSeq records. Three of the transcript variants are supported by experimental evidence and the fourth contains alternate 5' untranslated exons, the exact combination of which have not been experimentally confirmed for the full-length transcript. [provided by RefSeq, Oct 2015]

SCN1A-AS1 (HGNC:54069): (SCN1A and SCN9A antisense RNA 1)

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001165963.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1A	NM_001165963.4	MANE Select	c.603-242T>G		intron	N/A	NP_001159435.1
	SCN1A	NM_001202435.3		c.603-242T>G		intron	N/A	NP_001189364.1
	SCN1A	NM_001353948.2		c.603-242T>G		intron	N/A	NP_001340877.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN1A	ENST00000674923.1	MANE Select	c.603-242T>G		intron	N/A	ENSP00000501589.1
	SCN1A	ENST00000303395.9	TSL:5	c.603-242T>G		intron	N/A	ENSP00000303540.4
	SCN1A	ENST00000375405.7	TSL:5	c.603-242T>G		intron	N/A	ENSP00000364554.3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000164 AC: 1 AN: 609756 Hom.: 0 AF XY: 0.00000306 AC XY: 1 AN XY: 327156

African (AFR) AF: 0.00 AC: 0 AN: 15868

American (AMR) AF: 0.00 AC: 0 AN: 29796

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 18166

East Asian (EAS) AF: 0.00 AC: 0 AN: 34472

South Asian (SAS) AF: 0.00 AC: 0 AN: 59146

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 48050

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 2426

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 370272

Other (OTH) AF: 0.0000317 AC: 1 AN: 31560

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	0.67
DANN	Benign	0.46
PhyloP100		-0.12

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: rs2217199; hg19: chr2-166909695;