Variant 2-236166255-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The ENST00000306318.5(GBX2):c.706G>T(p.Gly236Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000274 in 1,461,264 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 0.0000027 ( 0 hom. )

Consequence

GBX2
ENST00000306318.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.366

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.3443572).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GBX2	NM_001485.4 linkuse as main transcript	c.706G>T	p.Gly236Cys	missense_variant	2/2	ENST00000306318.5	NP_001476.2
GBX2	XM_047443907.1 linkuse as main transcript	c.706G>T	p.Gly236Cys	missense_variant	2/4		XP_047299863.1
GBX2	NM_001301687.2 linkuse as main transcript	c.*74G>T		3_prime_UTR_variant	3/3		NP_001288616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GBX2	ENST00000306318.5 linkuse as main transcript	c.706G>T	p.Gly236Cys	missense_variant	2/2	1	NM_001485.4	ENSP00000302251	P1
GBX2	ENST00000551105.1 linkuse as main transcript	c.*74G>T		3_prime_UTR_variant	3/3	1		ENSP00000448747
GBX2	ENST00000465889.1 linkuse as main transcript	n.375G>T		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000400

AC:

AN:

249928

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135418

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.000164

GnomAD4 exome

AF:

0.00000274

AC:

AN:

1461264

Hom.:

Cov.:

AF XY:

0.00000275

AC XY:

AN XY:

726946

show subpopulations

Gnomad4 AFR exome

AF:

0.0000597

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

Cov.:

Alfa

AF:

0.0000508

Hom.:

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

Mar 19, 2024

The c.706G>T (p.G236C) alteration is located in exon 2 (coding exon 2) of the GBX2 gene. This alteration results from a G to T substitution at nucleotide position 706, causing the glycine (G) at amino acid position 236 to be replaced by a cysteine (C). 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

0.093

BayesDel_addAF

Uncertain

0.057

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.71

Eigen

Benign

-0.44

Eigen_PC

Benign

-0.59

FATHMM_MKL

Benign

0.35

LIST_S2

Benign

0.53

M_CAP

Pathogenic

0.33

MetaRNN

Benign

0.34

MetaSVM

Uncertain

0.12

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

N;N

PrimateAI

Uncertain

0.54

PROVEAN

Uncertain

-3.5

REVEL

Benign

0.23

Sift

Benign

0.036

Sift4G

Uncertain

0.0050

Polyphen

0.97

Vest4

0.22

MutPred

0.25

Loss of MoRF binding (P = 0.1017);

MVP

0.89

ClinPred

0.30

GERP RS

-0.19

Varity_R

0.29

gMVP

0.31

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