ENST00000551105.1:c.661C>T

Variant names:

• chr2-236166337-G-A
• rs1351561443
• ENST00000551105.1:c.661C>T

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The ENST00000551105.1(GBX2):​c.661C>T​(p.Leu221Phe) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 10/17 in silico tools predict a benign outcome for this variant. 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. L221V) has been classified as Uncertain significance.

• Frequency: Genomes: not found (cov: 33)
• Consequence: GBX2 ENST00000551105.1 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 4.16
• Publications: 1 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 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.13621336).

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000551105.1. 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.624C>T	p.Ser208Ser	synonymous	Exon 2 of 2	NP_001476.2
	GBX2	NM_001301687.2		c.661C>T	p.Leu221Phe	missense	Exon 3 of 3	NP_001288616.1	F8VY47

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GBX2	ENST00000551105.1	TSL:1	c.661C>T	p.Leu221Phe	missense	Exon 3 of 3	ENSP00000448747.1	F8VY47
	GBX2	ENST00000306318.5	TSL:1 MANE Select	c.624C>T	p.Ser208Ser	synonymous	Exon 2 of 2	ENSP00000302251.4	P52951
	GBX2	ENST00000465889.1	TSL:1	n.293C>T		non_coding_transcript_exon	Exon 2 of 2

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000398 AC: 1 AN: 251392 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00000880

Gnomad OTH exome AF: 0.00

GnomAD4 exome Cov.: 32

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.070
CADD	Benign	15
DANN	Uncertain	0.99
Eigen	Benign	-0.029
Eigen_PC	Benign	0.10
FATHMM_MKL	Uncertain	0.92	D
LIST_S2	Benign	0.42	T
M_CAP	Benign	0.011	T
MetaRNN	Benign	0.14	T
MetaSVM	Benign	-0.98	T
PhyloP100		4.2
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.066
Sift	Pathogenic	0.0	D
Sift4G	Pathogenic	0.0	D
Polyphen		0.040	B
Vest4		0.31
MutPred		0.19		Gain of methylation at R216 (P = 0.1643)
MVP		0.69
ClinPred		0.87	D
GERP RS		4.3
Mutation Taster		=83/17	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: rs1351561443; hg19: chr2-237074980;