2-166204470-GAAAC-G

Position:

chr2-166204470-GAAAC-G

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBA1

The NM_001365536.1(SCN9A):c.4399-10_4399-7del variant causes a splice region, splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,507,680 control chromosomes in the GnomAD database, including 573,967 homozygotes. 1/1 splice prediction tools predict no significant impact on normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60110 hom., cov: 0)

Exomes 𝑓: 0.87 ( 513857 hom. )

Consequence

SCN9A
NM_001365536.1 splice_region, splice_polypyrimidine_tract, intron

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:15

Conservation

PhyloP100: 0.886

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 2-166204470-GAAAC-G is Benign according to our data. Variant chr2-166204470-GAAAC-G is described in ClinVar as [Benign]. Clinvar id is 167657.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-166204470-GAAAC-G is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.929 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
SCN9A	NM_001365536.1 linkuse as main transcript	c.4399-10_4399-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant		ENST00000642356.2	NP_001352465.1
SCN1A-AS1	NR_110260.1 linkuse as main transcript	n.611+4660_611+4663del		intron_variant, non_coding_transcript_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
SCN9A	ENST00000642356.2 linkuse as main transcript	c.4399-10_4399-7del		splice_region_variant, splice_polypyrimidine_tract_variant, intron_variant			NM_001365536.1	ENSP00000495601	P1	Q15858-1
SCN1A-AS1	ENST00000651574.1 linkuse as main transcript	n.1289+4660_1289+4663del		intron_variant, non_coding_transcript_variant

Frequencies

GnomAD3 genomes

AF:

0.890

AC:

134739

AN:

151410

Hom.:

60067

Cov.:

show subpopulations

Gnomad AFR

AF:

0.937

Gnomad AMI

AF:

0.867

Gnomad AMR

AF:

0.886

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.937

Gnomad SAS

AF:

0.828

Gnomad FIN

AF:

0.886

Gnomad MID

AF:

0.879

Gnomad NFE

AF:

0.863

Gnomad OTH

AF:

0.883

GnomAD3 exomes

AF:

0.881

AC:

195432

AN:

221844

Hom.:

86221

AF XY:

0.877

AC XY:

105885

AN XY:

120736

show subpopulations

Gnomad AFR exome

AF:

0.938

Gnomad AMR exome

AF:

0.903

Gnomad ASJ exome

AF:

0.911

Gnomad EAS exome

AF:

0.938

Gnomad SAS exome

AF:

0.837

Gnomad FIN exome

AF:

0.892

Gnomad NFE exome

AF:

0.864

Gnomad OTH exome

AF:

0.875

GnomAD4 exome

AF:

0.869

AC:

1178638

AN:

1356152

Hom.:

513857

AF XY:

0.868

AC XY:

586267

AN XY:

675432

show subpopulations

Gnomad4 AFR exome

AF:

0.937

Gnomad4 AMR exome

AF:

0.899

Gnomad4 ASJ exome

AF:

0.907

Gnomad4 EAS exome

AF:

0.940

Gnomad4 SAS exome

AF:

0.836

Gnomad4 FIN exome

AF:

0.894

Gnomad4 NFE exome

AF:

0.863

Gnomad4 OTH exome

AF:

0.878

GnomAD4 genome

AF:

0.890

AC:

134838

AN:

151528

Hom.:

60110

Cov.:

AF XY:

0.889

AC XY:

65760

AN XY:

74008

show subpopulations

Gnomad4 AFR

AF:

0.937

Gnomad4 AMR

AF:

0.886

Gnomad4 ASJ

AF:

0.910

Gnomad4 EAS

AF:

0.937

Gnomad4 SAS

AF:

0.826

Gnomad4 FIN

AF:

0.886

Gnomad4 NFE

AF:

0.863

Gnomad4 OTH

AF:

0.883

Alfa

AF:

0.884

Hom.:

10776

Bravo

AF:

0.895

Asia WGS

AF:

0.878

AC:

3027

AN:

3448

ClinVar

Significance: Benign

Submissions summary: Benign:15

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	Jan 27, 2014	- -
Benign, criteria provided, single submitter	clinical testing	Unidad de Genómica Garrahan, Hospital de Pediatría Garrahan	Jul 15, 2024	This variant is classified as Benign based on local population frequency. This variant was detected in 89% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 83. Only high quality variants are reported. -
Benign, no assertion criteria provided	clinical testing	Joint Genome Diagnostic Labs from Nijmegen and Maastricht, Radboudumc and MUMC+	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, University Medical Center Utrecht	-	- -
Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	Athena Diagnostics	May 06, 2018	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Mar 03, 2015	This variant is associated with the following publications: (PMID: 27884173, 17470132, 23129781) -

Paroxysmal extreme pain disorder

Benign:2

Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Jul 15, 2021	- -
Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jun 14, 2016	- -

Inherited Erythromelalgia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Illumina Laboratory Services, Illumina

Jun 14, 2016

- -

Primary erythromelalgia

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

Channelopathy-associated congenital insensitivity to pain, autosomal recessive

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Jul 15, 2021

- -

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

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over