2-236167682-C-G

Position:

• chr2-236167682-C-G

Variant summary

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

The ENST00000306318.5(GBX2):​c.290G>C​(p.Gly97Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency: Genomes: not found (cov: 32)
• Consequence: GBX2 ENST00000306318.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.29

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/exons	MANE	Protein	UniProt
GBX2	NM_001485.4	c.290G>C	p.Gly97Ala	missense_variant	1/2	ENST00000306318.5	NP_001476.2
GBX2	NM_001301687.2	c.290G>C	p.Gly97Ala	missense_variant	1/3		NP_001288616.1
GBX2	XM_047443907.1	c.290G>C	p.Gly97Ala	missense_variant	1/4		XP_047299863.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GBX2	ENST00000306318.5	c.290G>C	p.Gly97Ala	missense_variant	1/2	1	NM_001485.4	ENSP00000302251	P1
GBX2-AS1	ENST00000415226.1	n.223+13C>G		intron_variant, non_coding_transcript_variant		4

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.290G>C (p.G97A) alteration is located in exon 1 (coding exon 1) of the GBX2 gene. This alteration results from a G to C substitution at nucleotide position 290, causing the glycine (G) at amino acid position 97 to be replaced by an alanine (A). 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	Uncertain	0.50
BayesDel_addAF	Pathogenic	0.27	D
BayesDel_noAF	Pathogenic	0.15
CADD	Uncertain	24
DANN	Uncertain	1.0
DEOGEN2	Benign	0.32	T;.
Eigen	Benign	0.17
Eigen_PC	Uncertain	0.26
FATHMM_MKL	Pathogenic	0.98	D
LIST_S2	Benign	0.82	T;T
M_CAP	Pathogenic	0.81	D
MetaRNN	Uncertain	0.48	T;T
MetaSVM	Uncertain	0.58	D
MutationAssessor	Benign	1.8	L;.
MutationTaster	Benign	1.0	D;D
PrimateAI	Pathogenic	0.93	D
PROVEAN	Benign	-1.1	N;N
REVEL	Uncertain	0.54
Sift	Benign	0.36	T;D
Sift4G	Benign	0.37	T;T
Polyphen		0.60	P;D
Vest4		0.41
MutPred		0.27		Gain of glycosylation at S93 (P = 0.1572);Gain of glycosylation at S93 (P = 0.1572);
MVP		0.93
ClinPred		0.90	D
GERP RS		4.7
Varity_R		0.42
gMVP		0.60

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-237076325;