11-118166933-T-G

Variant names:

• chr11-118166933-T-G
• rs772336314
• NM_004588.5:c.602A>C

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2 BP4

The NM_004588.5(SCN2B):​c.602A>C​(p.Glu201Ala) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 32)
• Consequence: SCN2B NM_004588.5 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.68

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 1 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.33822376).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SCN2B	NM_004588.5	c.602A>C	p.Glu201Ala	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.602A>C	p.Glu201Ala	missense_variant	Exon 4 of 4	1	NM_004588.5	ENSP00000278947.5
SCN2B	ENST00000658882.1	n.*427A>C		non_coding_transcript_exon_variant	Exon 5 of 5			ENSP00000499572.1
SCN2B	ENST00000669850.1	n.844A>C		non_coding_transcript_exon_variant	Exon 4 of 4
SCN2B	ENST00000658882.1	n.*427A>C		3_prime_UTR_variant	Exon 5 of 5			ENSP00000499572.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.31
BayesDel_addAF	Pathogenic	0.18	D
BayesDel_noAF	Uncertain	0.020
CADD	Pathogenic	27
DANN	Uncertain	1.0
DEOGEN2	Uncertain	0.50	D
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.30
FATHMM_MKL	Uncertain	0.96	D
LIST_S2	Uncertain	0.86	D
M_CAP	Uncertain	0.17	D
MetaRNN	Benign	0.34	T
MetaSVM	Uncertain	0.65	D
MutationAssessor	Benign	2.0	M
PrimateAI	Uncertain	0.67	T
PROVEAN	Benign	-1.0	N
REVEL	Uncertain	0.54
Sift	Benign	0.056	T
Sift4G	Benign	0.10	T
Polyphen		0.48	P
Vest4		0.33
MutPred		0.11		Gain of catalytic residue at E201 (P = 0.0541);
MVP		0.85
MPC		0.40
ClinPred		0.96	D
GERP RS		5.0
Varity_R		0.17
gMVP		0.40

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: rs772336314; hg19: chr11-118037648;