11-118166903-T-C
Position:
Variant summary
Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2
The NM_004588.5(SCN2B):c.632A>G(p.Asp211Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000149 in 1,613,902 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Genomes: 𝑓 0.000020 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000014 ( 0 hom. )
Consequence
SCN2B
NM_004588.5 missense
NM_004588.5 missense
Scores
1
7
11
Clinical Significance
Conservation
PhyloP100: 5.01
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]
Genome browser will be placed here
ACMG classification
Classification made for transcript
Verdict is Likely_benign. Variant got -4 ACMG points.
BS2
High AC in GnomAdExome4 at 21 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
SCN2B | NM_004588.5 | c.632A>G | p.Asp211Gly | missense_variant | 4/4 | ENST00000278947.6 | NP_004579.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
SCN2B | ENST00000278947.6 | c.632A>G | p.Asp211Gly | missense_variant | 4/4 | 1 | NM_004588.5 | ENSP00000278947.5 | ||
SCN2B | ENST00000658882.1 | n.*457A>G | non_coding_transcript_exon_variant | 5/5 | ENSP00000499572.1 | |||||
SCN2B | ENST00000669850.1 | n.874A>G | non_coding_transcript_exon_variant | 4/4 | ||||||
SCN2B | ENST00000658882.1 | n.*457A>G | 3_prime_UTR_variant | 5/5 | ENSP00000499572.1 |
Frequencies
GnomAD3 genomes AF: 0.0000197 AC: 3AN: 152108Hom.: 0 Cov.: 32
GnomAD3 genomes
AF:
AC:
3
AN:
152108
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00000795 AC: 2AN: 251438Hom.: 0 AF XY: 0.00000736 AC XY: 1AN XY: 135894
GnomAD3 exomes
AF:
AC:
2
AN:
251438
Hom.:
AF XY:
AC XY:
1
AN XY:
135894
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.0000144 AC: 21AN: 1461794Hom.: 0 Cov.: 31 AF XY: 0.0000165 AC XY: 12AN XY: 727198
GnomAD4 exome
AF:
AC:
21
AN:
1461794
Hom.:
Cov.:
31
AF XY:
AC XY:
12
AN XY:
727198
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.0000197 AC: 3AN: 152108Hom.: 0 Cov.: 32 AF XY: 0.0000269 AC XY: 2AN XY: 74298
GnomAD4 genome
AF:
AC:
3
AN:
152108
Hom.:
Cov.:
32
AF XY:
AC XY:
2
AN XY:
74298
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
ExAC
AF:
AC:
2
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Uncertain significance
Submissions summary: Uncertain:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Variant of unknown significance Uncertain:1
Uncertain significance, no assertion criteria provided | literature only | OMIM | Jul 01, 2013 | - - |
Atrial fibrillation, familial, 14 Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 04, 2023 | In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. Experimental studies have shown that this missense change affects SCN2B function (PMID: 23559163, 28597987). An algorithm developed to predict the effect of missense changes on protein structure and function (PolyPhen-2) suggests that this variant is likely to be tolerated. ClinVar contains an entry for this variant (Variation ID: 60776). This missense change has been observed in individual(s) with Brugada syndrome (PMID: 23559163). This variant is present in population databases (rs587777023, gnomAD 0.002%). This sequence change replaces aspartic acid, which is acidic and polar, with glycine, which is neutral and non-polar, at codon 211 of the SCN2B protein (p.Asp211Gly). - |
not provided Uncertain:1
Uncertain significance, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Cardiovascular phenotype Uncertain:1
Uncertain significance, criteria provided, single submitter | clinical testing | Ambry Genetics | Aug 19, 2019 | The p.D211G variant (also known as c.632A>G), located in coding exon 4 of the SCN2B gene, results from an A to G substitution at nucleotide position 632. The aspartic acid at codon 211 is replaced by glycine, an amino acid with similar properties. This alteration was reported in a subject with Brugada syndrome, but was also seen in family members with nonspecific symptoms or who were unaffected (Riuró H et al. Hum. Mutat., 2013 Jul;34:961-6). This alteration may have an impact in protein function (Riuró H et al. Hum. Mutat., 2013 Jul;34:961-6; Dulsat G et al. Biol. Cell, 2017 Jul;109:273-291). This amino acid position is not well conserved in available vertebrate species, and glycine is the reference amino acid in other vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear. - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Uncertain
DEOGEN2
Benign
T
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Uncertain
D
LIST_S2
Benign
T
M_CAP
Pathogenic
D
MetaRNN
Uncertain
D
MetaSVM
Uncertain
D
MutationAssessor
Benign
N
PrimateAI
Benign
T
PROVEAN
Benign
N
REVEL
Uncertain
Sift
Uncertain
D
Sift4G
Uncertain
D
Polyphen
B
Vest4
MVP
MPC
ClinPred
T
GERP RS
Varity_R
gMVP
Splicing
Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at