11-118176407-G-T

Variant names:

• chr11-118176407-G-T
• rs878854711
• NM_004588.5:c.25C>A

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004588.5(SCN2B):​c.25C>A​(p.Arg9Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,804 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R9H) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 31)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCN2B NM_004588.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.13
• Publications: 0 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: Uncertain_significance. The variant received 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.25766158).

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.25C>A	p.Arg9Ser	missense	Exon 1 of 4	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.25C>A	p.Arg9Ser	missense	Exon 1 of 4	ENSP00000278947.5	O60939
	SCN2B	ENST00000658882.1		n.25C>A		non_coding_transcript_exon	Exon 1 of 5	ENSP00000499572.1	A0A590UJS3

Frequencies

GnomAD3 genomes Cov.: 31

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461804 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 727208

African (AFR) AF: 0.00 AC: 0 AN: 33478

American (AMR) AF: 0.00 AC: 0 AN: 44720

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26134

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.00 AC: 0 AN: 86254

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53408

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 8.99e-7 AC: 1 AN: 1111954

Other (OTH) AF: 0.00 AC: 0 AN: 60392

GnomAD4 genome Cov.: 31

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.14
BayesDel_addAF	Pathogenic	0.19	D
BayesDel_noAF	Uncertain	0.030
CADD	Benign	21
DANN	Uncertain	0.99
DEOGEN2	Benign	0.27	T
Eigen	Benign	-0.22
Eigen_PC	Benign	-0.0074
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.058	D
MetaRNN	Benign	0.26	T
MetaSVM	Uncertain	0.13	D
MutationAssessor	Benign	0.69	N
PhyloP100		4.1
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	1.1	N
REVEL	Uncertain	0.48
Sift	Benign	0.56	T
Sift4G	Benign	0.20	T
Polyphen		0.099	B
Vest4		0.44
MutPred		0.47		Gain of glycosylation at R9 (P = 0.0318)
MVP		0.99
MPC		0.28
ClinPred		0.46	T
GERP RS		5.0
PromoterAI		-0.11	Neutral
Varity_R		0.20
gMVP		0.69
Mutation Taster		=69/31	polymorphism

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs878854711; hg19: chr11-118047122;