rs753389706

Variant names:

• chr11-118167074-C-G
• rs753389706
• NM_004588.5:c.461G>C

Your query was ambiguous. Multiple possible variants found:

• chr11-118167074-C-G
• chr11-118167074-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004588.5(SCN2B):​c.461G>C​(p.Arg154Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000685 in 1,459,906 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: SCN2B NM_004588.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.88

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2B	NM_004588.5	c.461G>C	p.Arg154Pro	missense_variant	Exon 4 of 4	ENST00000278947.6	NP_004579.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SCN2B	ENST00000278947.6	c.461G>C	p.Arg154Pro	missense_variant	Exon 4 of 4	1	NM_004588.5	ENSP00000278947.5
SCN2B	ENST00000658882.1	n.*286G>C		non_coding_transcript_exon_variant	Exon 5 of 5			ENSP00000499572.1
SCN2B	ENST00000669850.1	n.703G>C		non_coding_transcript_exon_variant	Exon 4 of 4
SCN2B	ENST00000658882.1	n.*286G>C		3_prime_UTR_variant	Exon 5 of 5			ENSP00000499572.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000401 AC: 1 AN: 249106 Hom.: 0 AF XY: 0.00000742 AC XY: 1 AN XY: 134806

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000884

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 6.85e-7 AC: 1 AN: 1459906 Hom.: 0 Cov.: 31 AF XY: 0.00000138 AC XY: 1 AN XY: 726362

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.00

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.00

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 8.99e-7

Gnomad4 OTH exome AF: 0.00

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Uncertain	0.48
BayesDel_addAF	Pathogenic	0.43	D
BayesDel_noAF	Pathogenic	0.38
CADD	Pathogenic	29
DANN	Uncertain	1.0
DEOGEN2	Benign	0.28	T
Eigen	Uncertain	0.61
Eigen_PC	Uncertain	0.62
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Uncertain	0.93	D
M_CAP	Uncertain	0.21	D
MetaRNN	Uncertain	0.45	T
MetaSVM	Pathogenic	0.95	D
MutationAssessor	Uncertain	2.5	M
PrimateAI	Benign	0.45	T
PROVEAN	Benign	-0.39	N
REVEL	Uncertain	0.60
Sift	Benign	0.20	T
Sift4G	Uncertain	0.024	D
Polyphen		0.99	D
Vest4		0.40
MutPred		0.29		Gain of glycosylation at R154 (P = 0.0087);
MVP		0.99
MPC		0.98
ClinPred		0.90	D
GERP RS		5.0
Varity_R		0.36
gMVP		0.77

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

Other links and lift over

dbSNP: rs753389706; hg19: chr11-118037789;