rs602594

Variant names:

• chr11-118169895-C-T
• rs602594
• NM_004588.5:c.71-1144G>A

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004588.5(SCN2B):​c.71-1144G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.202 in 152,104 control chromosomes in the GnomAD database, including 7,489 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.20 (7489 hom., cov: 32)
• Consequence: SCN2B NM_004588.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0490
• Publications: 1 publications found

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: Labcorp Genetics (formerly Invitae), Ambry Genetics
• 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

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.96).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.58 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004588.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN2B	NM_004588.5	MANE Select	c.71-1144G>A		intron	N/A	NP_004579.1	Q5U0K8

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN2B	ENST00000278947.6	TSL:1 MANE Select	c.71-1144G>A		intron	N/A	ENSP00000278947.5	O60939
	SCN2B	ENST00000658882.1		n.174+424G>A		intron	N/A	ENSP00000499572.1	A0A590UJS3
	SCN2B	ENST00000665446.1		n.306+424G>A		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.202 AC: 30690 AN: 151986 Hom.: 7481 Cov.: 32

Gnomad AFR AF: 0.586

Gnomad AMI AF: 0.0329

Gnomad AMR AF: 0.113

Gnomad ASJ AF: 0.0766

Gnomad EAS AF: 0.199

Gnomad SAS AF: 0.0464

Gnomad FIN AF: 0.0304

Gnomad MID AF: 0.0601

Gnomad NFE AF: 0.0375

Gnomad OTH AF: 0.152

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.202 AC: 30752 AN: 152104 Hom.: 7489 Cov.: 32 AF XY: 0.197 AC XY: 14628 AN XY: 74368

African (AFR) AF: 0.586 AC: 24263 AN: 41402

American (AMR) AF: 0.112 AC: 1721 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.0766 AC: 266 AN: 3472

East Asian (EAS) AF: 0.200 AC: 1031 AN: 5164

South Asian (SAS) AF: 0.0456 AC: 220 AN: 4824

European-Finnish (FIN) AF: 0.0304 AC: 323 AN: 10616

Middle Eastern (MID) AF: 0.0612 AC: 18 AN: 294

European-Non Finnish (NFE) AF: 0.0375 AC: 2552 AN: 68008

Other (OTH) AF: 0.155 AC: 328 AN: 2114

Alfa AF: 0.131 Hom.: 537

Bravo AF: 0.228

Asia WGS AF: 0.146 AC: 508 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.96
CADD	Benign	2.0
DANN	Benign	0.39
PhyloP100		0.049
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: rs602594; hg19: chr11-118040610;