7-100676569-C-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 3P and 2B. PM2PP2BP4_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. 14/22 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

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.18

Publications

0 publications found

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]

GNB2 Gene-Disease associations (from GenCC):

neurodevelopmental disorder with hypotonia and dysmorphic facies
Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
sick sinus syndrome 4
Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

GNB2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP2

Missense variant in the gene, where a lot of missense mutations are associated with disease in ClinVar. The gene has 8 curated pathogenic missense variants (we use a threshold of 10). The gene has 1 curated benign missense variants. Gene score misZ: 3.214 (above the threshold of 3.09). Trascript score misZ: 3.0761 (below the threshold of 3.09). GenCC associations: The gene is linked to sick sinus syndrome 4, neurodevelopmental disorder with hypotonia and dysmorphic facies.

BP4

Computational evidence support a benign effect (MetaRNN=0.12190178).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_005273.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GNB2	NM_005273.4	MANE Select	c.92C>G	p.Thr31Ser	missense	Exon 3 of 10	NP_005264.2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
GNB2	ENST00000303210.9	TSL:1 MANE Select	c.92C>G	p.Thr31Ser	missense	Exon 3 of 10	ENSP00000305260.4	P62879-1
GNB2	ENST00000393924.1	TSL:1	c.92C>G	p.Thr31Ser	missense	Exon 2 of 9	ENSP00000377501.1	P62879-1
GNB2	ENST00000879679.1		c.92C>G	p.Thr31Ser	missense	Exon 3 of 10	ENSP00000549738.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

6.86e-7

AC:

AN:

1457826

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

725564

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33396

American (AMR)

AF:

0.00

AC:

AN:

44718

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26108

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39694

South Asian (SAS)

AF:

0.00

AC:

AN:

86204

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53322

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5766

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1108346

Other (OTH)

AF:

0.00

AC:

AN:

60272

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.65

CADD

Benign

(source)

DANN

Benign

0.85

DEOGEN2

Benign

0.049

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.22

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.82

M_CAP

Benign

0.0057

MetaRNN

Benign

0.12

MetaSVM

Benign

-0.91

MutationAssessor

Benign

-1.4

PhyloP100

4.2

PrimateAI

Uncertain

0.58

PROVEAN

Benign

0.46

REVEL

Benign

0.096

Sift

Benign

0.83

Sift4G

Benign

0.75

Polyphen

0.0

Vest4

0.13

MutPred

0.20

Gain of disorder (P = 0.0898)

MVP

0.21

MPC

1.1

ClinPred

0.63

GERP RS

4.3

PromoterAI

-0.023

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.10

gMVP

0.52

Mutation Taster

=90/10

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over