11-118168740-G-C

Variant names:

• chr11-118168740-G-C
• rs17121819
• NM_004588.5:c.82C>G

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.82C>G​(p.Arg28Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 13/22 in silico tools predict 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. R28Q) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 32)
• Consequence: SCN2B NM_004588.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.854
• 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: 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

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=0.15117887).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN2B	NM_004588.5	MANE Select	c.82C>G	p.Arg28Gly	missense	Exon 2 of 4	NP_004579.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	SCN2B	ENST00000278947.6	TSL:1 MANE Select	c.82C>G	p.Arg28Gly	missense	Exon 2 of 4	ENSP00000278947.5
	SCN2B	ENST00000658882.1		n.186C>G		non_coding_transcript_exon	Exon 3 of 5	ENSP00000499572.1
	SCN2B	ENST00000665446.1		n.318C>G		non_coding_transcript_exon	Exon 3 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.074
BayesDel_addAF	Uncertain	0.073	D
BayesDel_noAF	Benign	-0.13
CADD	Benign	13
DANN	Benign	0.97
DEOGEN2	Benign	0.23	T
Eigen	Benign	-0.83
Eigen_PC	Benign	-0.72
FATHMM_MKL	Benign	0.25	N
LIST_S2	Benign	0.66	T
M_CAP	Uncertain	0.10	D
MetaRNN	Benign	0.15	T
MetaSVM	Uncertain	-0.036	T
MutationAssessor	Benign	-0.34	N
PhyloP100		0.85
PrimateAI	Benign	0.26	T
PROVEAN	Benign	-0.22	N
REVEL	Uncertain	0.31
Sift	Benign	0.13	T
Sift4G	Benign	0.31	T
Polyphen		0.0060	B
Vest4		0.25
MutPred		0.53		Loss of methylation at R28 (P = 0.0454)
MVP		0.95
MPC		0.31
ClinPred		0.12	T
GERP RS		2.7
Varity_R		0.47
gMVP		0.49
Mutation Taster		=91/9	polymorphism

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: rs17121819; hg19: chr11-118039455;