2-236167521-C-G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001485.4(GBX2):​c.451G>C​(p.Gly151Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. G151C) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

GBX2
NM_001485.4 missense

Scores

3
9
7

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.62
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-AS1 (HGNC:55714): (GBX2 and ASB18 antisense RNA 1)

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GBX2NM_001485.4 linkc.451G>C p.Gly151Arg missense_variant Exon 1 of 2 ENST00000306318.5 NP_001476.2 P52951
GBX2NM_001301687.2 linkc.451G>C p.Gly151Arg missense_variant Exon 1 of 3 NP_001288616.1 F8VY47
GBX2XM_047443907.1 linkc.451G>C p.Gly151Arg missense_variant Exon 1 of 4 XP_047299863.1
GBX2-AS1NR_186035.1 linkn.80C>G non_coding_transcript_exon_variant Exon 1 of 2

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GBX2ENST00000306318.5 linkc.451G>C p.Gly151Arg missense_variant Exon 1 of 2 1 NM_001485.4 ENSP00000302251.4 P52951

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
34
GnomAD4 genome
Cov.:
32
Bravo
AF:
0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.30
BayesDel_addAF
Pathogenic
0.21
D
BayesDel_noAF
Uncertain
0.070
CADD
Uncertain
25
DANN
Uncertain
1.0
DEOGEN2
Benign
0.33
T;.
Eigen
Uncertain
0.36
Eigen_PC
Uncertain
0.38
FATHMM_MKL
Uncertain
0.96
D
LIST_S2
Benign
0.83
T;T
M_CAP
Pathogenic
0.85
D
MetaRNN
Uncertain
0.58
D;D
MetaSVM
Uncertain
0.59
D
MutationAssessor
Benign
2.0
M;.
PrimateAI
Pathogenic
0.95
D
PROVEAN
Benign
-0.93
N;N
REVEL
Uncertain
0.55
Sift
Uncertain
0.0010
D;D
Sift4G
Benign
0.15
T;D
Polyphen
0.96
D;D
Vest4
0.44
MutPred
0.24
Gain of solvent accessibility (P = 0.1319);Gain of solvent accessibility (P = 0.1319);
MVP
0.93
ClinPred
0.87
D
GERP RS
4.6
Varity_R
0.35
gMVP
0.62

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.

Other links and lift over

dbSNP: rs1411805510; hg19: chr2-237076164; API