11-118166849-G-A

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_004588.5(SCN2B):c.*38C>T variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.092 in 1,611,098 control chromosomes in the GnomAD database, including 7,315 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.095 (738 hom., cov: 32)
  • Exomes 𝑓: 0.092 (6577 hom.)
• Consequence: SCN2B NM_004588.5 3_prime_UTR
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.28

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 Benign. Variant got -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.81).
• BP6: Variant 11-118166849-G-A is Benign according to our data. Variant chr11-118166849-G-A is described in ClinVar as [Benign]. Clinvar id is 1296386.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0985 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
SCN2B	NM_004588.5	c.*38C>T		3_prime_UTR_variant	4/4	ENST00000278947.6

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
SCN2B	ENST00000278947.6	c.*38C>T		3_prime_UTR_variant	4/4	1	NM_004588.5	P1
SCN2B	ENST00000669850.1	n.928C>T		non_coding_transcript_exon_variant	4/4
SCN2B	ENST00000658882.1	c.*511C>T		3_prime_UTR_variant, NMD_transcript_variant	5/5

Frequencies

GnomAD3 genomes AF: 0.0955 AC: 14516 AN: 151958 Hom.: 738 Cov.: 32

Gnomad AFR AF: 0.101

Gnomad AMI AF: 0.105

Gnomad AMR AF: 0.0770

Gnomad ASJ AF: 0.123

Gnomad EAS AF: 0.0180

Gnomad SAS AF: 0.0841

Gnomad FIN AF: 0.127

Gnomad MID AF: 0.162

Gnomad NFE AF: 0.0960

Gnomad OTH AF: 0.103

GnomAD3 exomes AF: 0.0875 AC: 21894 AN: 250108 Hom.: 1111 AF XY: 0.0898 AC XY: 12152 AN XY: 135300

Gnomad AFR exome AF: 0.104

Gnomad AMR exome AF: 0.0479

Gnomad ASJ exome AF: 0.111

Gnomad EAS exome AF: 0.0211

Gnomad SAS exome AF: 0.0832

Gnomad FIN exome AF: 0.124

Gnomad NFE exome AF: 0.100

Gnomad OTH exome AF: 0.0990

GnomAD4 exome AF: 0.0917 AC: 133749 AN: 1459022 Hom.: 6577 Cov.: 30 AF XY: 0.0918 AC XY: 66636 AN XY: 725970

Gnomad4 AFR exome AF: 0.101

Gnomad4 AMR exome AF: 0.0508

Gnomad4 ASJ exome AF: 0.114

Gnomad4 EAS exome AF: 0.0126

Gnomad4 SAS exome AF: 0.0835

Gnomad4 FIN exome AF: 0.127

Gnomad4 NFE exome AF: 0.0938

Gnomad4 OTH exome AF: 0.0975

GnomAD4 genome AF: 0.0955 AC: 14516 AN: 152076 Hom.: 738 Cov.: 32 AF XY: 0.0968 AC XY: 7198 AN XY: 74326

Gnomad4 AFR AF: 0.101

Gnomad4 AMR AF: 0.0769

Gnomad4 ASJ AF: 0.123

Gnomad4 EAS AF: 0.0178

Gnomad4 SAS AF: 0.0835

Gnomad4 FIN AF: 0.127

Gnomad4 NFE AF: 0.0960

Gnomad4 OTH AF: 0.102

Alfa AF: 0.0989 Hom.: 182

Bravo AF: 0.0904

Asia WGS AF: 0.0490 AC: 170 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 13, 2018

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	6.8
Dann	Benign	0.60

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs8192614; hg19: chr11-118037564; COSMIC: COSV54050410;