rs8192613

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_004588.5(SCN2B):c.449-12C>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.483 in 1,607,468 control chromosomes in the GnomAD database, including 191,531 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.46 ( 16819 hom., cov: 32)

Exomes 𝑓: 0.49 ( 174712 hom. )

Consequence

SCN2B
NM_004588.5 intron

Scores

Splicing: ADA: 0.0002714

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:8

Conservation

PhyloP100: 0.332

Publications

11 publications found

Variant links:

Genes affected

SCN2B (HGNC:10589): (sodium voltage-gated channel beta subunit 2) The protein encoded by this gene is the beta 2 subunit of the type II voltage-gated sodium channel. The encoded protein is involved in cell-cell adhesion and cell migration. Defects in this gene can be a cause of Brugada Syndrome, atrial fibrillation, or sudden infant death syndrome. [provided by RefSeq, Jul 2015]

SCN2B Gene-Disease associations (from GenCC):

atrial fibrillation, familial, 14
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae)
Brugada syndrome
Inheritance: AD Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Genomics England PanelApp
familial atrial fibrillation
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
Brugada syndrome 1
Inheritance: AD Classification: NO_KNOWN Submitted by: ClinGen

SCN2B links:

ENSG00000309913 (HGNC:):

ENSG00000309913 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.83).

BP6

Variant 11-118167098-G-T is Benign according to our data. Variant chr11-118167098-G-T is described in ClinVar as Benign. ClinVar VariationId is 259446.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2B	NM_004588.5 link	c.449-12C>A		intron_variant	Intron 3 of 3	ENST00000278947.6	NP_004579.1	O60939Q5U0K8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN2B	ENST00000278947.6 link	c.449-12C>A		intron_variant	Intron 3 of 3	1	NM_004588.5	ENSP00000278947.5		O60939

Frequencies

GnomAD3 genomes

AF:

0.462

AC:

70140

AN:

151890

Hom.:

16804

Cov.:

show subpopulations

Gnomad AFR

AF:

0.361

Gnomad AMI

AF:

0.447

Gnomad AMR

AF:

0.497

Gnomad ASJ

AF:

0.552

Gnomad EAS

AF:

0.766

Gnomad SAS

AF:

0.547

Gnomad FIN

AF:

0.567

Gnomad MID

AF:

0.430

Gnomad NFE

AF:

0.465

Gnomad OTH

AF:

0.467

GnomAD2 exomes

AF:

0.505

AC:

123691

AN:

244966

AF XY:

0.509

show subpopulations

Gnomad AFR exome

AF:

0.359

Gnomad AMR exome

AF:

0.484

Gnomad ASJ exome

AF:

0.543

Gnomad EAS exome

AF:

0.776

Gnomad FIN exome

AF:

0.544

Gnomad NFE exome

AF:

0.467

Gnomad OTH exome

AF:

0.498

GnomAD4 exome

AF:

0.486

AC:

706813

AN:

1455462

Hom.:

174712

Cov.:

AF XY:

0.488

AC XY:

353632

AN XY:

724196

show subpopulations

African (AFR)

AF:

0.349

AC:

11667

AN:

33432

American (AMR)

AF:

0.485

AC:

21632

AN:

44634

Ashkenazi Jewish (ASJ)

AF:

0.547

AC:

14284

AN:

26124

East Asian (EAS)

AF:

0.770

AC:

30553

AN:

39678

South Asian (SAS)

AF:

0.554

AC:

47771

AN:

86222

European-Finnish (FIN)

AF:

0.541

AC:

26164

AN:

48354

Middle Eastern (MID)

AF:

0.462

AC:

2663

AN:

5766

European-Non Finnish (NFE)

AF:

0.470

AC:

521696

AN:

1110954

Other (OTH)

AF:

0.504

AC:

30383

AN:

60298

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

17726

35453

53179

70906

88632

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

15766

31532

47298

63064

78830

<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:

0.462

AC:

70195

AN:

152006

Hom.:

16819

Cov.:

AF XY:

0.470

AC XY:

34897

AN XY:

74312

show subpopulations

African (AFR)

AF:

0.361

AC:

14971

AN:

41460

American (AMR)

AF:

0.498

AC:

7605

AN:

15282

Ashkenazi Jewish (ASJ)

AF:

0.552

AC:

1911

AN:

3464

East Asian (EAS)

AF:

0.765

AC:

3942

AN:

5150

South Asian (SAS)

AF:

0.546

AC:

2629

AN:

4816

European-Finnish (FIN)

AF:

0.567

AC:

6003

AN:

10578

Middle Eastern (MID)

AF:

0.446

AC:

131

AN:

294

European-Non Finnish (NFE)

AF:

0.465

AC:

31601

AN:

67948

Other (OTH)

AF:

0.473

AC:

995

AN:

2104

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.497

Heterozygous variant carriers

1855

3710

5566

7421

9276

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

654

1308

1962

2616

3270

<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:

0.467

Hom.:

5016

Bravo

AF:

0.456

Asia WGS

AF:

0.636

AC:

2207

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:8

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:5

Clinical Genetics, Academic Medical Center

Significance:Benign

Review Status:no assertion criteria provided

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

- -

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 06, 2016

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Apr 04, 2023

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Atrial fibrillation, familial, 14

Benign:2

Jul 15, 2021

Genome-Nilou Lab

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Feb 03, 2025

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.83

CADD

Benign

(source)

DANN

Benign

0.59

PhyloP100

0.33

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00027

dbscSNV1_RF

Benign

0.034

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