Variant 2-236166184-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The ENST00000306318.5(GBX2):c.777G>A(p.Leu259=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00412 in 1,613,972 control chromosomes in the GnomAD database, including 270 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.021 ( 122 hom., cov: 33)

Exomes 𝑓: 0.0023 ( 148 hom. )

Consequence

GBX2
ENST00000306318.5 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 0.236

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.48).

BP6

Variant 2-236166184-C-T is Benign according to our data. Variant chr2-236166184-C-T is described in ClinVar as [Benign]. Clinvar id is 780367.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=0.236 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0724 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
GBX2	NM_001485.4 linkuse as main transcript	c.777G>A	p.Leu259=	synonymous_variant	2/2	ENST00000306318.5	NP_001476.2
GBX2	XM_047443907.1 linkuse as main transcript	c.777G>A	p.Leu259=	synonymous_variant	2/4		XP_047299863.1
GBX2	NM_001301687.2 linkuse as main transcript	c.*145G>A		3_prime_UTR_variant	3/3		NP_001288616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris
GBX2	ENST00000306318.5 linkuse as main transcript	c.777G>A	p.Leu259=	synonymous_variant	2/2	1	NM_001485.4	ENSP00000302251	P1
GBX2	ENST00000551105.1 linkuse as main transcript	c.*145G>A		3_prime_UTR_variant	3/3	1		ENSP00000448747
GBX2	ENST00000465889.1 linkuse as main transcript	n.446G>A		non_coding_transcript_exon_variant	2/2	1

Frequencies

GnomAD3 genomes

AF:

0.0214

AC:

3258

AN:

152224

Hom.:

123

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0748

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00713

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000414

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000191

Gnomad OTH

AF:

0.0163

GnomAD3 exomes

AF:

0.00552

AC:

1383

AN:

250752

Hom.:

AF XY:

0.00410

AC XY:

557

AN XY:

135720

show subpopulations

Gnomad AFR exome

AF:

0.0773

Gnomad AMR exome

AF:

0.00318

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000196

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000971

Gnomad OTH exome

AF:

0.00294

GnomAD4 exome

AF:

0.00232

AC:

3390

AN:

1461630

Hom.:

148

Cov.:

AF XY:

0.00200

AC XY:

1451

AN XY:

727136

show subpopulations

Gnomad4 AFR exome

AF:

0.0840

Gnomad4 AMR exome

AF:

0.00338

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000209

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000621

Gnomad4 OTH exome

AF:

0.00522

GnomAD4 genome

AF:

0.0214

AC:

3259

AN:

152342

Hom.:

122

Cov.:

AF XY:

0.0206

AC XY:

1534

AN XY:

74504

show subpopulations

Gnomad4 AFR

AF:

0.0746

Gnomad4 AMR

AF:

0.00712

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000191

Gnomad4 OTH

AF:

0.0161

Alfa

AF:

0.0120

Hom.:

Bravo

AF:

0.0247

Asia WGS

AF:

0.00375

AC:

AN:

3478

EpiCase

AF:

0.000109

EpiControl

AF:

0.000119

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.48

CADD

Benign

8.1

DANN

Benign

0.94

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over