2-236167521-C-G

Variant names:

• chr2-236167521-C-G
• rs1411805510
• NM_001485.4:c.451G>C

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.62

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)

ACMG classification

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
GBX2	NM_001485.4	c.451G>C	p.Gly151Arg	missense_variant	Exon 1 of 2	ENST00000306318.5	NP_001476.2
GBX2	NM_001301687.2	c.451G>C	p.Gly151Arg	missense_variant	Exon 1 of 3		NP_001288616.1
GBX2	XM_047443907.1	c.451G>C	p.Gly151Arg	missense_variant	Exon 1 of 4		XP_047299863.1
GBX2-AS1	NR_186035.1	n.80C>G		non_coding_transcript_exon_variant	Exon 1 of 2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GBX2	ENST00000306318.5	c.451G>C	p.Gly151Arg	missense_variant	Exon 1 of 2	1	NM_001485.4	ENSP00000302251.4

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

Other links and lift over

dbSNP: rs1411805510; hg19: chr2-237076164;