2-166293380-C-G

Variant names:

• chr2-166293380-C-G
• rs199942413
• NM_001365536.1:c.966-8G>C

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_Strong BP6_Moderate

The NM_001365536.1(SCN9A):​c.966-8G>C variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000762 in 1,444,362 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 3/3 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000076 (0 hom.)
• Consequence: SCN9A NM_001365536.1 splice_region, intron
• Scores: Splicing: ADA: 0.00001571
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -2.91
• Publications: 0 publications found

Genes affected

SCN9A (HGNC:10597): (sodium voltage-gated channel alpha subunit 9) This gene encodes a voltage-gated sodium channel which plays a significant role in nociception signaling. Mutations in this gene have been associated with primary erythermalgia, channelopathy-associated insensitivity to pain, and paroxysmal extreme pain disorder. [provided by RefSeq, Aug 2009]

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

ACMG classification

Our verdict: Likely_benign. The variant received -6 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.85).
• BP6: Variant 2-166293380-C-G is Benign according to our data. Variant chr2-166293380-C-G is described in ClinVar as Likely_benign. ClinVar VariationId is 1083044.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001365536.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	NM_001365536.1	MANE Select	c.966-8G>C		splice_region intron	N/A	NP_001352465.1	Q15858-1
	SCN9A	NM_002977.4		c.966-8G>C		splice_region intron	N/A	NP_002968.2	Q15858-3
	SCN1A-AS1	NR_110260.1		n.1030-1185C>G		intron	N/A

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN9A	ENST00000642356.2	MANE Select	c.966-8G>C		splice_region intron	N/A	ENSP00000495601.1	Q15858-1
	SCN9A	ENST00000303354.11	TSL:5	c.966-8G>C		splice_region intron	N/A	ENSP00000304748.7	Q15858-1
	SCN9A	ENST00000409672.5	TSL:5	c.966-8G>C		splice_region intron	N/A	ENSP00000386306.1	Q15858-3

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000762 AC: 11 AN: 1444362 Hom.: 0 Cov.: 31 AF XY: 0.00000698 AC XY: 5 AN XY: 716778

African (AFR) AF: 0.00 AC: 0 AN: 33090

American (AMR) AF: 0.00 AC: 0 AN: 42878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25398

East Asian (EAS) AF: 0.0000254 AC: 1 AN: 39382

South Asian (SAS) AF: 0.00 AC: 0 AN: 82798

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 52854

Middle Eastern (MID) AF: 0.000176 AC: 1 AN: 5682

European-Non Finnish (NFE) AF: 0.00000816 AC: 9 AN: 1102616

Other (OTH) AF: 0.00 AC: 0 AN: 59664

GnomAD4 genome Cov.: 32

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.85
CADD	Benign	0.067
DANN	Benign	0.55
PhyloP100		-2.9
Mutation Taster		=100/0	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
dbscSNV1_ADA	Benign	0.000016
dbscSNV1_RF	Benign	0.0040
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: rs199942413; hg19: chr2-167149890;