chr2-166281810-T-TA

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

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

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:13

Conservation

PhyloP100: -0.261

Publications

4 publications found

Variant links:

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]

SCN9A links:

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

SCN1A-AS1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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 rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1 link	c.1975-3dupT		splice_region_variant, intron_variant	Intron 12 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein
SCN9A	ENST00000642356.2 link	c.1975-3_1975-2insT	splice_region_variant, intron_variant	Intron 12 of 26		NM_001365536.1	ENSP00000495601.1
SCN9A	ENST00000303354.11 link	c.1975-3_1975-2insT	splice_region_variant, intron_variant	Intron 12 of 26	5		ENSP00000304748.7
SCN9A	ENST00000409672.5 link	c.1942-3_1942-2insT	splice_region_variant, intron_variant	Intron 12 of 26	5		ENSP00000386306.1
SCN9A	ENST00000645907.1 link	c.1942-3_1942-2insT	splice_region_variant, intron_variant	Intron 12 of 26			ENSP00000495983.1
SCN9A	ENST00000454569.6 link	c.1942-3_1942-2insT	splice_region_variant, intron_variant	Intron 12 of 14	1		ENSP00000413212.2

Frequencies

GnomAD3 genomes

AF:

0.0690

AC:

10299

AN:

149218

Hom.:

411

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.0930

AC:

13856

AN:

148910

AF XY:

0.0953

show subpopulations

Gnomad AFR exome

AF:

0.0813

Gnomad AMR exome

AF:

0.0736

Gnomad ASJ exome

AF:

0.179

Gnomad EAS exome

AF:

0.0305

Gnomad FIN exome

AF:

0.101

Gnomad NFE exome

AF:

0.0995

Gnomad OTH exome

AF:

0.113

GnomAD4 exome

AF:

0.0809

AC:

100070

AN:

1237090

Hom.:

1223

Cov.:

AF XY:

0.0813

AC XY:

49907

AN XY:

613726

show subpopulations

African (AFR)

AF:

0.0727

AC:

1978

AN:

27218

American (AMR)

AF:

0.0513

AC:

1710

AN:

33328

Ashkenazi Jewish (ASJ)

AF:

0.126

AC:

2656

AN:

21098

East Asian (EAS)

AF:

0.0508

AC:

1631

AN:

32106

South Asian (SAS)

AF:

0.0643

AC:

4417

AN:

68710

European-Finnish (FIN)

AF:

0.0756

AC:

3364

AN:

44476

Middle Eastern (MID)

AF:

0.120

AC:

602

AN:

5008

European-Non Finnish (NFE)

AF:

0.0832

AC:

79476

AN:

954910

Other (OTH)

AF:

0.0843

AC:

4236

AN:

50236

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.429

Heterozygous variant carriers

4189

8378

12568

16757

20946

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

3006

6012

9018

12024

15030

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0690

AC:

10308

AN:

149308

Hom.:

411

Cov.:

AF XY:

0.0681

AC XY:

4960

AN XY:

72860

show subpopulations

African (AFR)

AF:

0.0587

AC:

2397

AN:

40824

American (AMR)

AF:

0.0686

AC:

1024

AN:

14934

Ashkenazi Jewish (ASJ)

AF:

0.115

AC:

396

AN:

3432

East Asian (EAS)

AF:

0.0221

AC:

113

AN:

5124

South Asian (SAS)

AF:

0.0462

AC:

217

AN:

4698

European-Finnish (FIN)

AF:

0.0729

AC:

723

AN:

9924

Middle Eastern (MID)

AF:

0.145

AC:

AN:

290

European-Non Finnish (NFE)

AF:

0.0761

AC:

5104

AN:

67094

Other (OTH)

AF:

0.0797

AC:

166

AN:

2084

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.494

Heterozygous variant carriers

455

910

1366

1821

2276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

116

232

348

464

580

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0500

Hom.:

Bravo

AF:

0.0667

ClinVar

Significance: Benign

Submissions summary: Benign:13

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

May 07, 2018

Athena Diagnostics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Mar 03, 2015

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

not specified

Benign:1

Mar 12, 2014

Eurofins Ntd Llc (ga)

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

Inherited Erythromelalgia

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Neuropathy, hereditary sensory and autonomic, type 2A

Benign:1

May 28, 2019

Mendelics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

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

Benign:1

Mar 18, 2016

Soonchunhyang University Bucheon Hospital, Soonchunhyang University Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:reference population

Generalized epilepsy with febrile seizures plus

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 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Congenital Indifference to Pain

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Small fiber neuropathy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Paroxysmal extreme pain disorder

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Febrile seizures, familial

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Severe myoclonic epilepsy in infancy

Benign:1

Jun 14, 2016

Illumina Laboratory Services, Illumina

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

PhyloP100

-0.26

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over