Variant 2-236167566-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001485.4(GBX2):c.406G>C(p.Gly136Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000796 in 1,597,906 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00053 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00082 ( 1 hom. )

Consequence

GBX2
NM_001485.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.763

Variant links:

Genes affected

GBX2 (HGNC:4186): (gastrulation brain homeobox 2) Enables sequence-specific double-stranded DNA binding activity. Predicted to be involved in regulation of nervous system development and regulation of transcription by RNA polymerase II. Predicted to act upstream of or within several processes, including branching involved in blood vessel morphogenesis; nervous system development; and neural crest cell migration. Predicted to be part of chromatin. Predicted to be active in nucleus. [provided by Alliance of Genome Resources, Apr 2022]

GBX2 links:

GBX2-AS1 (HGNC:):

GBX2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.14743325).

BS2

High AC in GnomAd4 at 81 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GBX2	NM_001485.4 linkuse as main transcript	c.406G>C	p.Gly136Arg	missense_variant	1/2	ENST00000306318.5	NP_001476.2	P52951
GBX2	NM_001301687.2 linkuse as main transcript	c.406G>C	p.Gly136Arg	missense_variant	1/3		NP_001288616.1	F8VY47
GBX2	XM_047443907.1 linkuse as main transcript	c.406G>C	p.Gly136Arg	missense_variant	1/4		XP_047299863.1
GBX2-AS1	NR_186035.1 linkuse as main transcript	n.125C>G		non_coding_transcript_exon_variant	1/2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBX2	ENST00000306318.5 linkuse as main transcript	c.406G>C	p.Gly136Arg	missense_variant	1/2	1	NM_001485.4	ENSP00000302251.4		P52951

Frequencies

GnomAD3 genomes

AF:

0.000533

AC:

AN:

152092

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000483

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000327

Gnomad ASJ

AF:

0.000288

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.000378

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000985

Gnomad OTH

AF:

0.000479

GnomAD3 exomes

AF:

0.000571

AC:

124

AN:

217158

Hom.:

AF XY:

0.000498

AC XY:

AN XY:

120538

show subpopulations

Gnomad AFR exome

AF:

0.0000842

Gnomad AMR exome

AF:

0.000334

Gnomad ASJ exome

AF:

0.000869

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000174

Gnomad FIN exome

AF:

0.000591

Gnomad NFE exome

AF:

0.000912

Gnomad OTH exome

AF:

0.000367

GnomAD4 exome

AF:

0.000824

AC:

1191

AN:

1445706

Hom.:

Cov.:

AF XY:

0.000801

AC XY:

576

AN XY:

718796

show subpopulations

Gnomad4 AFR exome

AF:

0.000124

Gnomad4 AMR exome

AF:

0.000341

Gnomad4 ASJ exome

AF:

0.00101

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000377

Gnomad4 FIN exome

AF:

0.000671

Gnomad4 NFE exome

AF:

0.000924

Gnomad4 OTH exome

AF:

0.000937

GnomAD4 genome

AF:

0.000532

AC:

AN:

152200

Hom.:

Cov.:

AF XY:

0.000417

AC XY:

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.0000481

Gnomad4 AMR

AF:

0.000327

Gnomad4 ASJ

AF:

0.000288

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.000378

Gnomad4 NFE

AF:

0.000985

Gnomad4 OTH

AF:

0.000474

Alfa

AF:

0.000909

Hom.:

Bravo

AF:

0.000457

TwinsUK

AF:

0.00

AC:

ALSPAC

AF:

0.00130

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000596

AC:

ExAC

AF:

0.000479

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jun 18, 2021

The c.406G>C (p.G136R) alteration is located in exon 1 (coding exon 1) of the GBX2 gene. This alteration results from a G to C substitution at nucleotide position 406, causing the glycine (G) at amino acid position 136 to be replaced by an arginine (R). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.30

BayesDel_addAF

Benign

-0.15

BayesDel_noAF

Uncertain

-0.020

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.21

T;.

Eigen

Benign

0.18

Eigen_PC

Uncertain

0.27

FATHMM_MKL

Uncertain

0.97

LIST_S2

Benign

0.75

T;T

M_CAP

Pathogenic

0.87

MetaRNN

Benign

0.15

T;T

MetaSVM

Uncertain

0.10

MutationAssessor

Benign

0.0

N;.

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

0.53

N;N

REVEL

Uncertain

0.49

Sift

Benign

0.21

T;D

Sift4G

Benign

0.30

T;D

Polyphen

0.97

D;D

Vest4

0.43

MVP

0.95

ClinPred

0.13

GERP RS

4.6

Varity_R

0.22

gMVP

0.35

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over