Variant chr2-120972110-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001374353.1(GLI2):c.1182+47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.969 in 1,609,734 control chromosomes in the GnomAD database, including 759,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.89 ( 61867 hom., cov: 35)

Exomes 𝑓: 0.98 ( 697720 hom. )

Consequence

GLI2
NM_001374353.1 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.55

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BP6

Variant 2-120972110-T-C is Benign according to our data. Variant chr2-120972110-T-C is described in ClinVar as [Benign]. Clinvar id is 259710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.98 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.1182+47T>C		intron_variant		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.1182+47T>C		intron_variant		1	NM_001374353.1	ENSP00000354586	P2

Frequencies

GnomAD3 genomes

AF:

0.890

AC:

135379

AN:

152156

Hom.:

61849

Cov.:

show subpopulations

Gnomad AFR

AF:

0.650

Gnomad AMI

AF:

0.997

Gnomad AMR

AF:

0.942

Gnomad ASJ

AF:

0.966

Gnomad EAS

AF:

1.00

Gnomad SAS

AF:

0.981

Gnomad FIN

AF:

0.996

Gnomad MID

AF:

0.943

Gnomad NFE

AF:

0.986

Gnomad OTH

AF:

0.918

GnomAD3 exomes

AF:

0.962

AC:

237340

AN:

246640

Hom.:

115077

AF XY:

0.968

AC XY:

129988

AN XY:

134266

show subpopulations

Gnomad AFR exome

AF:

0.638

Gnomad AMR exome

AF:

0.972

Gnomad ASJ exome

AF:

0.969

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.979

Gnomad FIN exome

AF:

0.995

Gnomad NFE exome

AF:

0.987

Gnomad OTH exome

AF:

0.967

GnomAD4 exome

AF:

0.977

AC:

1423825

AN:

1457460

Hom.:

697720

Cov.:

AF XY:

0.978

AC XY:

709225

AN XY:

725214

show subpopulations

Gnomad4 AFR exome

AF:

0.631

Gnomad4 AMR exome

AF:

0.969

Gnomad4 ASJ exome

AF:

0.969

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.979

Gnomad4 FIN exome

AF:

0.995

Gnomad4 NFE exome

AF:

0.987

Gnomad4 OTH exome

AF:

0.962

GnomAD4 genome

AF:

0.889

AC:

135445

AN:

152274

Hom.:

61867

Cov.:

AF XY:

0.893

AC XY:

66448

AN XY:

74450

show subpopulations

Gnomad4 AFR

AF:

0.650

Gnomad4 AMR

AF:

0.942

Gnomad4 ASJ

AF:

0.966

Gnomad4 EAS

AF:

1.00

Gnomad4 SAS

AF:

0.981

Gnomad4 FIN

AF:

0.996

Gnomad4 NFE

AF:

0.986

Gnomad4 OTH

AF:

0.919

Alfa

AF:

0.939

Hom.:

12602

Bravo

AF:

0.873

Asia WGS

AF:

0.969

AC:

3370

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Nov 12, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

1.2

DANN

Benign

0.62

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