Variant chr2-120955465-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 ENST00000361492.9(GLI2):c.643+35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 1,364,864 control chromosomes in the GnomAD database, including 584,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.79 ( 52061 hom., cov: 33)

Exomes 𝑓: 0.93 ( 532376 hom. )

Consequence

GLI2
ENST00000361492.9 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.895

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=-0.85).

BP6

Variant 2-120955465-T-C is Benign according to our data. Variant chr2-120955465-T-C is described in ClinVar as [Benign]. Clinvar id is 259733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 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.643+35T>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.643+35T>C		intron_variant		1	NM_001374353.1	ENSP00000354586	P2

Frequencies

GnomAD3 genomes

AF:

0.788

AC:

119839

AN:

152068

Hom.:

52058

Cov.:

show subpopulations

Gnomad AFR

AF:

0.380

Gnomad AMI

AF:

0.995

Gnomad AMR

AF:

0.886

Gnomad ASJ

AF:

0.886

Gnomad EAS

AF:

0.999

Gnomad SAS

AF:

0.957

Gnomad FIN

AF:

0.979

Gnomad MID

AF:

0.867

Gnomad NFE

AF:

0.947

Gnomad OTH

AF:

0.840

GnomAD3 exomes

AF:

0.913

AC:

142153

AN:

155738

Hom.:

66452

AF XY:

0.922

AC XY:

77584

AN XY:

84144

show subpopulations

Gnomad AFR exome

AF:

0.373

Gnomad AMR exome

AF:

0.934

Gnomad ASJ exome

AF:

0.879

Gnomad EAS exome

AF:

1.00

Gnomad SAS exome

AF:

0.951

Gnomad FIN exome

AF:

0.973

Gnomad NFE exome

AF:

0.946

Gnomad OTH exome

AF:

0.918

GnomAD4 exome

AF:

0.932

AC:

1130477

AN:

1212678

Hom.:

532376

Cov.:

AF XY:

0.934

AC XY:

564548

AN XY:

604172

show subpopulations

Gnomad4 AFR exome

AF:

0.347

Gnomad4 AMR exome

AF:

0.927

Gnomad4 ASJ exome

AF:

0.888

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.953

Gnomad4 FIN exome

AF:

0.974

Gnomad4 NFE exome

AF:

0.947

Gnomad4 OTH exome

AF:

0.904

GnomAD4 genome

AF:

0.788

AC:

119866

AN:

152186

Hom.:

52061

Cov.:

AF XY:

0.795

AC XY:

59147

AN XY:

74416

show subpopulations

Gnomad4 AFR

AF:

0.380

Gnomad4 AMR

AF:

0.886

Gnomad4 ASJ

AF:

0.886

Gnomad4 EAS

AF:

0.999

Gnomad4 SAS

AF:

0.957

Gnomad4 FIN

AF:

0.979

Gnomad4 NFE

AF:

0.947

Gnomad4 OTH

AF:

0.841

Alfa

AF:

0.847

Hom.:

12111

Bravo

AF:

0.762

Asia WGS

AF:

0.932

AC:

3242

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Apr 12, 2019	- -
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

- -

Holoprosencephaly 9

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

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

-0.85

CADD

Benign

0.36

DANN

Benign

0.42

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