rs6432893

Variant names:

• chr2-166280609-G-A
• rs6432893
• NM_001365536.1:c.2105-14C>T

Your query was ambiguous. Multiple possible variants found:

• chr2-166280609-G-A
• chr2-166280609-G-C
• chr2-166280609-G-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001365536.1(SCN9A):​c.2105-14C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.49 in 1,494,214 control chromosomes in the GnomAD database, including 182,629 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.56 (24870 hom., cov: 33)
  • Exomes 𝑓: 0.48 (157759 hom.)
• Consequence: SCN9A NM_001365536.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:15
• Conservation: PhyloP100: -0.857
• Publications: 11 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: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BP6: Variant 2-166280609-G-A is Benign according to our data. Variant chr2-166280609-G-A is described in ClinVar as Benign. ClinVar VariationId is 167659.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.747 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1	c.2105-14C>T		intron_variant	Intron 13 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2	c.2105-14C>T		intron_variant	Intron 13 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11	c.2105-14C>T		intron_variant	Intron 13 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5	c.2072-14C>T		intron_variant	Intron 13 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1	c.2072-14C>T		intron_variant	Intron 13 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6	c.2072-14C>T		intron_variant	Intron 13 of 14	1		ENSP00000413212.2

Frequencies

GnomAD3 genomes AF: 0.557 AC: 84640 AN: 151914 Hom.: 24832 Cov.: 33

Gnomad AFR AF: 0.754

Gnomad AMI AF: 0.316

Gnomad AMR AF: 0.526

Gnomad ASJ AF: 0.500

Gnomad EAS AF: 0.377

Gnomad SAS AF: 0.435

Gnomad FIN AF: 0.486

Gnomad MID AF: 0.446

Gnomad NFE AF: 0.485

Gnomad OTH AF: 0.548

GnomAD2 exomes AF: 0.493 AC: 79755 AN: 161820 AF XY: 0.484

Gnomad AFR exome AF: 0.761

Gnomad AMR exome AF: 0.532

Gnomad ASJ exome AF: 0.506

Gnomad EAS exome AF: 0.376

Gnomad FIN exome AF: 0.489

Gnomad NFE exome AF: 0.478

Gnomad OTH exome AF: 0.485

GnomAD4 exome AF: 0.482 AC: 646768 AN: 1342182 Hom.: 157759 Cov.: 21 AF XY: 0.480 AC XY: 319087 AN XY: 665116

African (AFR) AF: 0.767 AC: 23397 AN: 30506

American (AMR) AF: 0.526 AC: 18618 AN: 35402

Ashkenazi Jewish (ASJ) AF: 0.506 AC: 12348 AN: 24412

East Asian (EAS) AF: 0.383 AC: 13997 AN: 36580

South Asian (SAS) AF: 0.442 AC: 34174 AN: 77370

European-Finnish (FIN) AF: 0.482 AC: 23793 AN: 49332

Middle Eastern (MID) AF: 0.458 AC: 2539 AN: 5546

European-Non Finnish (NFE) AF: 0.477 AC: 490303 AN: 1027006

Other (OTH) AF: 0.493 AC: 27599 AN: 56028

GnomAD4 genome AF: 0.557 AC: 84741 AN: 152032 Hom.: 24870 Cov.: 33 AF XY: 0.552 AC XY: 41049 AN XY: 74308

African (AFR) AF: 0.754 AC: 31281 AN: 41502

American (AMR) AF: 0.525 AC: 8013 AN: 15264

Ashkenazi Jewish (ASJ) AF: 0.500 AC: 1734 AN: 3470

East Asian (EAS) AF: 0.378 AC: 1945 AN: 5146

South Asian (SAS) AF: 0.436 AC: 2106 AN: 4828

European-Finnish (FIN) AF: 0.486 AC: 5130 AN: 10548

Middle Eastern (MID) AF: 0.462 AC: 135 AN: 292

European-Non Finnish (NFE) AF: 0.485 AC: 32956 AN: 67958

Other (OTH) AF: 0.545 AC: 1153 AN: 2114

Alfa AF: 0.449 Hom.: 2281

Bravo AF: 0.566

Asia WGS AF: 0.444 AC: 1551 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:5

-

Genome Diagnostics Laboratory, University Medical Center Utrecht

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Jul 24, 2017

Eurofins Ntd Llc (ga)

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jul 15, 2024

Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as Benign based on local population frequency. This variant was detected in 67% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 62. Only high quality variants are reported. -

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance: Benign

Review Status: no assertion criteria provided

Collection Method: clinical testing

- -

Primary erythromelalgia Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Channelopathy-associated congenital insensitivity to pain, autosomal recessive Benign:2

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not provided Benign:2

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Paroxysmal extreme pain disorder Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Jan 13, 2018

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -

Inherited Erythromelalgia Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

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

Feb 04, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	0.13
DANN	Benign	0.53
PhyloP100		-0.86
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: rs6432893; hg19: chr2-167137119; COSMIC: COSV57600629; COSMIC: COSV57600629;