2-120989853-A-G

Position:

chr2-120989853-A-G

Variant summary

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

The NM_001374353.1(GLI2):c.3888A>G(p.Pro1296Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.69 in 1,611,978 control chromosomes in the GnomAD database, including 391,025 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.61 ( 30061 hom., cov: 35)

Exomes 𝑓: 0.70 ( 360964 hom. )

Consequence

GLI2
NM_001374353.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:11

Conservation

PhyloP100: -0.00400

Variant links:

Genes affected

GLI2 (HGNC:4318): (GLI family zinc finger 2) This gene encodes a protein which belongs to the C2H2-type zinc finger protein subclass of the Gli family. Members of this subclass are characterized as transcription factors which bind DNA through zinc finger motifs. These motifs contain conserved H-C links. Gli family zinc finger proteins are mediators of Sonic hedgehog (Shh) signaling and they are implicated as potent oncogenes in the embryonal carcinoma cell. The protein encoded by this gene localizes to the cytoplasm and activates patched Drosophila homolog (PTCH) gene expression. It is also thought to play a role during embryogenesis. The encoded protein is associated with several phenotypes- Greig cephalopolysyndactyly syndrome, Pallister-Hall syndrome, preaxial polydactyly type IV, postaxial polydactyly types A1 and B. [provided by RefSeq, Jul 2008]

GLI2 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=-0.8).

BP6

Variant 2-120989853-A-G is Benign according to our data. Variant chr2-120989853-A-G is described in ClinVar as [Benign]. Clinvar id is 95273.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-120989853-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=-0.004 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.729 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI2	NM_001374353.1 linkuse as main transcript	c.3888A>G	p.Pro1296Pro	synonymous_variant	14/14	ENST00000361492.9	NP_001361282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI2	ENST00000361492.9 linkuse as main transcript	c.3888A>G	p.Pro1296Pro	synonymous_variant	14/14	1	NM_001374353.1	ENSP00000354586.5		A0A7I2PJA1

Frequencies

GnomAD3 genomes

AF:

0.612

AC:

93110

AN:

152034

Hom.:

30053

Cov.:

show subpopulations

Gnomad AFR

AF:

0.407

Gnomad AMI

AF:

0.801

Gnomad AMR

AF:

0.630

Gnomad ASJ

AF:

0.674

Gnomad EAS

AF:

0.488

Gnomad SAS

AF:

0.507

Gnomad FIN

AF:

0.670

Gnomad MID

AF:

0.690

Gnomad NFE

AF:

0.735

Gnomad OTH

AF:

0.639

GnomAD3 exomes

AF:

0.636

AC:

157209

AN:

247246

Hom.:

51603

AF XY:

0.640

AC XY:

86046

AN XY:

134360

show subpopulations

Gnomad AFR exome

AF:

0.395

Gnomad AMR exome

AF:

0.573

Gnomad ASJ exome

AF:

0.669

Gnomad EAS exome

AF:

0.474

Gnomad SAS exome

AF:

0.525

Gnomad FIN exome

AF:

0.683

Gnomad NFE exome

AF:

0.732

Gnomad OTH exome

AF:

0.668

GnomAD4 exome

AF:

0.698

AC:

1018503

AN:

1459828

Hom.:

360964

Cov.:

AF XY:

0.694

AC XY:

503895

AN XY:

726154

show subpopulations

Gnomad4 AFR exome

AF:

0.394

Gnomad4 AMR exome

AF:

0.577

Gnomad4 ASJ exome

AF:

0.674

Gnomad4 EAS exome

AF:

0.495

Gnomad4 SAS exome

AF:

0.526

Gnomad4 FIN exome

AF:

0.679

Gnomad4 NFE exome

AF:

0.736

Gnomad4 OTH exome

AF:

0.667

GnomAD4 genome

AF:

0.612

AC:

93126

AN:

152150

Hom.:

30061

Cov.:

AF XY:

0.608

AC XY:

45217

AN XY:

74384

show subpopulations

Gnomad4 AFR

AF:

0.407

Gnomad4 AMR

AF:

0.629

Gnomad4 ASJ

AF:

0.674

Gnomad4 EAS

AF:

0.488

Gnomad4 SAS

AF:

0.506

Gnomad4 FIN

AF:

0.670

Gnomad4 NFE

AF:

0.735

Gnomad4 OTH

AF:

0.641

Alfa

AF:

0.677

Hom.:

15307

Bravo

AF:

0.598

Asia WGS

AF:

0.492

AC:

1712

AN:

3478

EpiCase

AF:

0.739

EpiControl

AF:

0.740

ClinVar

Significance: Benign

Submissions summary: Benign:11

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not specified

Benign:4

Benign, criteria provided, single submitter	clinical testing	PreventionGenetics, part of Exact Sciences	-	- -
Benign, no assertion criteria provided	clinical testing	Clinical Genetics, Academic Medical Center	-	- -
Benign, criteria provided, single submitter	clinical testing	Eurofins Ntd Llc (ga)	May 09, 2013	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -

not provided

Benign:3

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 28, 2018	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Nov 29, 2023	- -

Holoprosencephaly 9

Benign:2

Benign, criteria provided, single submitter	clinical testing	Illumina Laboratory Services, Illumina	Jan 13, 2018	This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. -
Benign, criteria provided, single submitter	clinical testing	Genome-Nilou Lab	Aug 10, 2021	- -

Holoprosencephaly 9;C4014479:Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Labcorp Genetics (formerly Invitae), Labcorp

Feb 01, 2024

- -

Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.80

CADD

Benign

0.98

DANN

Benign

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

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