chr2-236167521-C-G

Variant names:

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

Variant summary

Our verdict is Uncertain significance. The variant received 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
• Publications: 0 publications found

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

Our verdict: Uncertain_significance. The variant received 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001485.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBX2	NM_001485.4	MANE Select	c.451G>C	p.Gly151Arg	missense	Exon 1 of 2	NP_001476.2
	GBX2	NM_001301687.2		c.451G>C	p.Gly151Arg	missense	Exon 1 of 3	NP_001288616.1	F8VY47
	GBX2-AS1	NR_186035.1		n.80C>G		non_coding_transcript_exon	Exon 1 of 2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBX2	ENST00000306318.5	TSL:1 MANE Select	c.451G>C	p.Gly151Arg	missense	Exon 1 of 2	ENSP00000302251.4	P52951
	GBX2	ENST00000551105.1	TSL:1	c.451G>C	p.Gly151Arg	missense	Exon 1 of 3	ENSP00000448747.1	F8VY47
	GBX2-AS1	ENST00000415226.1	TSL:4	n.75C>G		non_coding_transcript_exon	Exon 1 of 4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000756

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

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
M_CAP	Pathogenic	0.85	D
MetaRNN	Uncertain	0.58	D
MetaSVM	Uncertain	0.59	D
MutationAssessor	Benign	2.0	M
PhyloP100		2.6
PrimateAI	Pathogenic	0.95	D
PROVEAN	Benign	-0.93	N
REVEL	Uncertain	0.55
Sift	Uncertain	0.0010	D
Sift4G	Benign	0.15	T
Polyphen		0.96	D
Vest4		0.44
MutPred		0.24		Gain of solvent accessibility (P = 0.1319)
MVP		0.93
ClinPred		0.87	D
GERP RS		4.6
PromoterAI		-0.055	Neutral
Varity_R		0.35
gMVP		0.62
Mutation Taster		=69/31	polymorphism

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

Other links and lift over

dbSNP: rs1411805510; hg19: chr2-237076164;