Variant chr2-236167808-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -4 ACMG points: 0P and 4B. BS2

The NM_001485.4(GBX2):c.164T>C(p.Leu55Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000423 in 1,417,982 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.0000066 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000039 ( 0 hom. )

Consequence

GBX2
NM_001485.4 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.73

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:55714): (GBX2 and ASB18 antisense RNA 1)

GBX2-AS1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Likely_benign. Variant got -4 ACMG points.

BS2

High AC in GnomAdExome4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
GBX2	NM_001485.4 linkuse as main transcript	c.164T>C	p.Leu55Pro	missense_variant	1/2	ENST00000306318.5
GBX2	NM_001301687.2 linkuse as main transcript	c.164T>C	p.Leu55Pro	missense_variant	1/3
GBX2	XM_047443907.1 linkuse as main transcript	c.164T>C	p.Leu55Pro	missense_variant	1/4

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GBX2	ENST00000306318.5 linkuse as main transcript	c.164T>C	p.Leu55Pro	missense_variant	1/2	1	NM_001485.4	P1
GBX2-AS1	ENST00000415226.1 linkuse as main transcript	n.223+139A>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes

AF:

0.00000662

AC:

AN:

151154

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000148

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.00000395

AC:

AN:

1266828

Hom.:

Cov.:

AF XY:

0.00000482

AC XY:

AN XY:

621842

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000145

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

AF:

0.00000662

AC:

AN:

151154

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

73812

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000148

Gnomad4 OTH

AF:

0.00

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 09, 2023

The c.164T>C (p.L55P) alteration is located in exon 1 (coding exon 1) of the GBX2 gene. This alteration results from a T to C substitution at nucleotide position 164, causing the leucine (L) at amino acid position 55 to be replaced by a proline (P). 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

0.79

BayesDel_addAF

Pathogenic

0.31

BayesDel_noAF

Pathogenic

0.21

CADD

Pathogenic

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.47

T;.

Eigen

Uncertain

0.46

Eigen_PC

Uncertain

0.47

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.73

T;T

M_CAP

Pathogenic

0.97

MetaRNN

Uncertain

0.73

D;D

MetaSVM

Uncertain

0.74

MutationAssessor

Uncertain

2.1

M;.

MutationTaster

Benign

1.0

D;D

PrimateAI

Pathogenic

0.95

PROVEAN

Benign

-0.94

N;D

REVEL

Uncertain

0.63

Sift

Pathogenic

0.0

D;D

Sift4G

Uncertain

0.057

T;T

Polyphen

1.0

D;D

Vest4

0.48

MutPred

0.16

Gain of glycosylation at L55 (P = 0.0037);Gain of glycosylation at L55 (P = 0.0037);

MVP

0.92

ClinPred

0.97

GERP RS

4.7

Varity_R

0.76

gMVP

0.46

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