Variant 2-236166032-G-T 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.929C>A(p.Ala310Asp) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,862 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: 6.8e-7 ( 0 hom. )

Consequence

GBX2
ENST00000306318.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.84

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:

Genome browser will be placed here

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=0.35378897).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GBX2	NM_001485.4 linkuse as main transcript	c.929C>A	p.Ala310Asp	missense_variant	2/2	ENST00000306318.5	NP_001476.2
GBX2	XM_047443907.1 linkuse as main transcript	c.929C>A	p.Ala310Asp	missense_variant	2/4		XP_047299863.1
GBX2	NM_001301687.2 linkuse as main transcript	c.*297C>A		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.929C>A	p.Ala310Asp	missense_variant	2/2	1	NM_001485.4	ENSP00000302251	P1
GBX2	ENST00000551105.1 linkuse as main transcript	c.*297C>A		3_prime_UTR_variant	3/3	1		ENSP00000448747
GBX2	ENST00000465889.1 linkuse as main transcript	n.598C>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD3 exomes

AF:

0.00000398

AC:

AN:

251478

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135916

show subpopulations

Gnomad AFR exome

AF:

0.0000615

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:

0.00

GnomAD4 exome

AF:

6.84e-7

AC:

AN:

1461862

Hom.:

Cov.:

AF XY:

0.00000138

AC XY:

AN XY:

727230

show subpopulations

Gnomad4 AFR exome

AF:

0.0000299

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:

0.00

GnomAD4 genome

Cov.:

Bravo

AF:

0.00000378

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

Nov 01, 2021

The c.929C>A (p.A310D) alteration is located in exon 2 (coding exon 2) of the GBX2 gene. This alteration results from a C to A substitution at nucleotide position 929, causing the alanine (A) at amino acid position 310 to be replaced by an aspartic acid (D). 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

Pathogenic

0.96

BayesDel_addAF

Benign

-0.022

BayesDel_noAF

Benign

-0.090

CADD

Pathogenic

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.48

Eigen

Benign

0.025

Eigen_PC

Benign

0.17

FATHMM_MKL

Uncertain

0.90

LIST_S2

Benign

0.86

M_CAP

Uncertain

0.14

MetaRNN

Benign

0.35

MetaSVM

Uncertain

-0.0073

MutationAssessor

Benign

0.55

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.86

PROVEAN

Uncertain

-2.8

REVEL

Uncertain

0.44

Sift

Benign

0.090

Sift4G

Uncertain

0.013

Polyphen

0.57

Vest4

0.37

MutPred

0.28

Loss of MoRF binding (P = 0.057);

MVP

0.81

ClinPred

0.57

GERP RS

4.7

Varity_R

0.57

gMVP

0.90

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