Variant chr2-120982929-C-T 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.1632+49C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.926 in 1,586,752 control chromosomes in the GnomAD database, including 692,339 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.80 ( 52888 hom., cov: 33)

Exomes 𝑓: 0.94 ( 639451 hom. )

Consequence

GLI2
NM_001374353.1 intron

Scores

Clinical Significance

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

Conservation

PhyloP100: 0.290

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=-0.86).

BP6

Variant 2-120982929-C-T is Benign according to our data. Variant chr2-120982929-C-T is described in ClinVar as [Benign]. Clinvar id is 259717.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.975 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.1632+49C>T		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.1632+49C>T		intron_variant		1	NM_001374353.1	ENSP00000354586.5		A0A7I2PJA1

Frequencies

GnomAD3 genomes

AF:

0.798

AC:

121294

AN:

152060

Hom.:

52882

Cov.:

show subpopulations

Gnomad AFR

AF:

0.406

Gnomad AMI

AF:

0.993

Gnomad AMR

AF:

0.875

Gnomad ASJ

AF:

0.874

Gnomad EAS

AF:

0.998

Gnomad SAS

AF:

0.946

Gnomad FIN

AF:

0.991

Gnomad MID

AF:

0.854

Gnomad NFE

AF:

0.954

Gnomad OTH

AF:

0.834

GnomAD3 exomes

AF:

0.916

AC:

221664

AN:

241978

Hom.:

103974

AF XY:

0.927

AC XY:

121333

AN XY:

130958

show subpopulations

Gnomad AFR exome

AF:

0.392

Gnomad AMR exome

AF:

0.937

Gnomad ASJ exome

AF:

0.881

Gnomad EAS exome

AF:

0.999

Gnomad SAS exome

AF:

0.943

Gnomad FIN exome

AF:

0.990

Gnomad NFE exome

AF:

0.953

Gnomad OTH exome

AF:

0.926

GnomAD4 exome

AF:

0.940

AC:

1348400

AN:

1434574

Hom.:

639451

Cov.:

AF XY:

0.942

AC XY:

669606

AN XY:

711156

show subpopulations

Gnomad4 AFR exome

AF:

0.386

Gnomad4 AMR exome

AF:

0.930

Gnomad4 ASJ exome

AF:

0.882

Gnomad4 EAS exome

AF:

1.00

Gnomad4 SAS exome

AF:

0.943

Gnomad4 FIN exome

AF:

0.989

Gnomad4 NFE exome

AF:

0.956

Gnomad4 OTH exome

AF:

0.910

GnomAD4 genome

AF:

0.797

AC:

121329

AN:

152178

Hom.:

52888

Cov.:

AF XY:

0.805

AC XY:

59881

AN XY:

74398

show subpopulations

Gnomad4 AFR

AF:

0.406

Gnomad4 AMR

AF:

0.875

Gnomad4 ASJ

AF:

0.874

Gnomad4 EAS

AF:

0.998

Gnomad4 SAS

AF:

0.946

Gnomad4 FIN

AF:

0.991

Gnomad4 NFE

AF:

0.954

Gnomad4 OTH

AF:

0.836

Alfa

AF:

0.868

Hom.:

19476

Bravo

AF:

0.771

Asia WGS

AF:

0.926

AC:

3219

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

-0.86

CADD

Benign

2.9

DANN

Benign

0.48

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