7-100676569-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_005273.4(GNB2):​c.92C>G​(p.Thr31Ser) variant causes a missense change. The variant allele was found at a frequency of 0.000000686 in 1,457,826 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 13/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 6.9e-7 ( 0 hom. )

Consequence

GNB2
NM_005273.4 missense

Scores

2
17

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18
Variant links:
Genes affected
GNB2 (HGNC:4398): (G protein subunit beta 2) Heterotrimeric guanine nucleotide-binding proteins (G proteins), which integrate signals between receptors and effector proteins, are composed of an alpha, a beta, and a gamma subunit. These subunits are encoded by families of related genes. This gene encodes a beta subunit. Beta subunits are important regulators of alpha subunits, as well as of certain signal transduction receptors and effectors. This gene contains a trinucleotide (CCG) repeat length polymorphism in its 5' UTR. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.12190178).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GNB2NM_005273.4 linkc.92C>G p.Thr31Ser missense_variant Exon 3 of 10 ENST00000303210.9 NP_005264.2 P62879-1Q6FHM2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GNB2ENST00000303210.9 linkc.92C>G p.Thr31Ser missense_variant Exon 3 of 10 1 NM_005273.4 ENSP00000305260.4 P62879-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
6.86e-7
AC:
1
AN:
1457826
Hom.:
0
Cov.:
29
AF XY:
0.00
AC XY:
0
AN XY:
725564
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.0000252
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Nov 01, 2023
CeGaT Center for Human Genetics Tuebingen
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

GNB2: PM2, PP2, BP4 -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.061
BayesDel_addAF
Benign
-0.29
T
BayesDel_noAF
Benign
-0.65
CADD
Benign
21
DANN
Benign
0.85
DEOGEN2
Benign
0.049
T;.;T;T;.;T
Eigen
Benign
-0.48
Eigen_PC
Benign
-0.22
FATHMM_MKL
Uncertain
0.97
D
LIST_S2
Benign
0.82
.;T;.;T;T;T
M_CAP
Benign
0.0057
T
MetaRNN
Benign
0.12
T;T;T;T;T;T
MetaSVM
Benign
-0.91
T
MutationAssessor
Benign
-1.4
N;.;N;.;.;N
PrimateAI
Uncertain
0.58
T
PROVEAN
Benign
0.46
N;N;N;N;N;N
REVEL
Benign
0.096
Sift
Benign
0.83
T;T;T;T;T;T
Sift4G
Benign
0.75
T;T;T;T;T;T
Polyphen
0.0
B;.;B;.;.;B
Vest4
0.13
MutPred
0.20
Gain of disorder (P = 0.0898);Gain of disorder (P = 0.0898);Gain of disorder (P = 0.0898);Gain of disorder (P = 0.0898);Gain of disorder (P = 0.0898);Gain of disorder (P = 0.0898);
MVP
0.21
MPC
1.1
ClinPred
0.63
D
GERP RS
4.3
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.0
Varity_R
0.10
gMVP
0.52

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

Below is the list of publications found by LitVar. It may be empty.

Other links and lift over

dbSNP: rs1324648019; hg19: chr7-100274192; API