2-166281810-TA-TAA

Position:

• chr2-166281810-TA-TAA

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_Strong BA1

The NM_001365536.1(SCN9A):​c.1975-3dupT variant causes a splice region, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0796 in 1,386,398 control chromosomes in the GnomAD database, including 1,634 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.069 (411 hom., cov: 31)
  • Exomes 𝑓: 0.081 (1223 hom.)
• Consequence: SCN9A NM_001365536.1 splice_region, intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:13
• Conservation: PhyloP100: -0.261

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:):

ACMG classification

Verdict is Benign. Variant got -16 ACMG points.

• BP6: Variant 2-166281810-T-TA is Benign according to our data. Variant chr2-166281810-T-TA is described in ClinVar as [Benign]. Clinvar id is 167661.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.0743 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.1975-3dupT		splice_region_variant, intron_variant		ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.1975-3dupT		splice_region_variant, intron_variant			NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.1975-3dupT		splice_region_variant, intron_variant		5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.1942-3dupT		splice_region_variant, intron_variant		5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.1942-3dupT		splice_region_variant, intron_variant				ENSP00000495983.1
SCN9A	ENST00000454569.6	c.1942-3dupT		splice_region_variant, intron_variant		1		ENSP00000413212.2

Frequencies

GnomAD3 genomes AF: 0.0690 AC: 10299 AN: 149218 Hom.: 411 Cov.: 31

Gnomad AFR AF: 0.0586

Gnomad AMI AF: 0.139

Gnomad AMR AF: 0.0688

Gnomad ASJ AF: 0.115

Gnomad EAS AF: 0.0220

Gnomad SAS AF: 0.0458

Gnomad FIN AF: 0.0729

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.0761

Gnomad OTH AF: 0.0803

GnomAD4 exome AF: 0.0809 AC: 100070 AN: 1237090 Hom.: 1223 Cov.: 29 AF XY: 0.0813 AC XY: 49907 AN XY: 613726

Gnomad4 AFR exome AF: 0.0727

Gnomad4 AMR exome AF: 0.0513

Gnomad4 ASJ exome AF: 0.126

Gnomad4 EAS exome AF: 0.0508

Gnomad4 SAS exome AF: 0.0643

Gnomad4 FIN exome AF: 0.0756

Gnomad4 NFE exome AF: 0.0832

Gnomad4 OTH exome AF: 0.0843

GnomAD4 genome AF: 0.0690 AC: 10308 AN: 149308 Hom.: 411 Cov.: 31 AF XY: 0.0681 AC XY: 4960 AN XY: 72860

Gnomad4 AFR AF: 0.0587

Gnomad4 AMR AF: 0.0686

Gnomad4 ASJ AF: 0.115

Gnomad4 EAS AF: 0.0221

Gnomad4 SAS AF: 0.0462

Gnomad4 FIN AF: 0.0729

Gnomad4 NFE AF: 0.0761

Gnomad4 OTH AF: 0.0797

Bravo AF: 0.0667

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	- -
Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 07, 2018	- -

not specified Benign:1

Benign, no assertion criteria provided

clinical testing

Eurofins Ntd Llc (ga)

Mar 12, 2014

- -

Inherited Erythromelalgia Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Neuropathy, hereditary sensory and autonomic, type 2A Benign:1

Benign, criteria provided, single submitter

clinical testing

Mendelics

May 28, 2019

- -

Primary erythromelalgia;C0751122:Severe myoclonic epilepsy in infancy;C2751778:Generalized epilepsy with febrile seizures plus, type 7 Benign:1

Benign, criteria provided, single submitter

reference population

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

Mar 18, 2016

- -

Generalized epilepsy with febrile seizures plus Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Generalized epilepsy with febrile seizures plus, type 7;C2752089:Neuropathy, hereditary sensory and autonomic, type 2A Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Congenital Indifference to Pain Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Small fiber neuropathy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Paroxysmal extreme pain disorder Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Febrile seizures, familial Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Severe myoclonic epilepsy in infancy Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

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: rs35888674; hg19: chr2-167138320;