2-166203939-A-T

Variant names:

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001365536.1(SCN9A):c.4774+16T>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.871 in 1,446,268 control chromosomes in the GnomAD database, including 549,682 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 60405 hom., cov: 33)

Exomes 𝑓: 0.87 ( 489277 hom. )

Consequence

SCN9A
NM_001365536.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:9

Conservation

PhyloP100: -0.0760

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.82).

BP6

Variant 2-166203939-A-T is Benign according to our data. Variant chr2-166203939-A-T is described in ClinVar as [Benign]. Clinvar id is 258888.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-166203939-A-T is described in Lovd as [Benign].

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.93 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN9A	NM_001365536.1 link	c.4774+16T>A		intron_variant	Intron 26 of 26	ENST00000642356.2	NP_001352465.1

Ensembl

Gene	Transcript	HGVSc	Effect	Exon rank	TSL	MANE	Protein	UniProt
SCN9A	ENST00000642356.2 link	c.4774+16T>A	intron_variant	Intron 26 of 26		NM_001365536.1	ENSP00000495601.1	Q15858-1
SCN9A	ENST00000303354.11 link	c.4774+16T>A	intron_variant	Intron 26 of 26	5		ENSP00000304748.7	Q15858-1
SCN9A	ENST00000409672.5 link	c.4741+16T>A	intron_variant	Intron 26 of 26	5		ENSP00000386306.1	Q15858-3
SCN9A	ENST00000645907.1 link	c.4741+16T>A	intron_variant	Intron 26 of 26			ENSP00000495983.1	Q15858-4

Frequencies

GnomAD3 genomes

AF:

0.891

AC:

135255

AN:

151834

Hom.:

60362

Cov.:

show subpopulations

Gnomad AFR

AF:

0.937

Gnomad AMI

AF:

0.868

Gnomad AMR

AF:

0.886

Gnomad ASJ

AF:

0.910

Gnomad EAS

AF:

0.951

Gnomad SAS

AF:

0.830

Gnomad FIN

AF:

0.888

Gnomad MID

AF:

0.883

Gnomad NFE

AF:

0.863

Gnomad OTH

AF:

0.883

GnomAD3 exomes

AF:

0.883

AC:

158939

AN:

179950

Hom.:

70302

AF XY:

0.880

AC XY:

85274

AN XY:

96918

show subpopulations

Gnomad AFR exome

AF:

0.938

Gnomad AMR exome

AF:

0.906

Gnomad ASJ exome

AF:

0.910

Gnomad EAS exome

AF:

0.953

Gnomad SAS exome

AF:

0.842

Gnomad FIN exome

AF:

0.892

Gnomad NFE exome

AF:

0.863

Gnomad OTH exome

AF:

0.875

GnomAD4 exome

AF:

0.869

AC:

1124794

AN:

1294316

Hom.:

489277

Cov.:

AF XY:

0.868

AC XY:

560294

AN XY:

645254

show subpopulations

Gnomad4 AFR exome

AF:

0.937

Gnomad4 AMR exome

AF:

0.902

Gnomad4 ASJ exome

AF:

0.907

Gnomad4 EAS exome

AF:

0.949

Gnomad4 SAS exome

AF:

0.839

Gnomad4 FIN exome

AF:

0.895

Gnomad4 NFE exome

AF:

0.863

Gnomad4 OTH exome

AF:

0.877

GnomAD4 genome

AF:

0.891

AC:

135354

AN:

151952

Hom.:

60405

Cov.:

AF XY:

0.890

AC XY:

66080

AN XY:

74276

show subpopulations

Gnomad4 AFR

AF:

0.937

Gnomad4 AMR

AF:

0.886

Gnomad4 ASJ

AF:

0.910

Gnomad4 EAS

AF:

0.950

Gnomad4 SAS

AF:

0.830

Gnomad4 FIN

AF:

0.888

Gnomad4 NFE

AF:

0.863

Gnomad4 OTH

AF:

0.882

Alfa

AF:

0.886

Hom.:

10973

Bravo

AF:

0.896

Asia WGS

AF:

0.886

AC:

3078

AN:

3474

ClinVar

Significance: Benign

Submissions summary: Benign:9

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:3

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 95% of patients studied in a panel designed for Epileptic and Developmental Encephalopathy and Progressive Myoclonus Epilepsy. Number of patients: 88. 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

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Mar 03, 2015

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Primary erythromelalgia

Benign:1

Jul 15, 2021

Genome-Nilou Lab

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Channelopathy-associated congenital insensitivity to pain, autosomal recessive

Benign:1

Jul 15, 2021

Genome-Nilou Lab

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

- -

Paroxysmal extreme pain disorder

Benign:1

Jul 15, 2021

Genome-Nilou Lab

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

-0.82

CADD

Benign

9.3

DANN

Benign

0.80

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

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