Variant rs116523674 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_001374353.1(GLI2):c.1317+25C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0263 in 1,611,900 control chromosomes in the GnomAD database, including 661 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.029 ( 94 hom., cov: 34)

Exomes 𝑓: 0.026 ( 567 hom. )

Consequence

GLI2
NM_001374353.1 intron

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -1.75

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=-0.93).

BP6

Variant 2-120975134-C-T is Benign according to our data. Variant chr2-120975134-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 259711.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0293 (4461/152334) while in subpopulation AFR AF= 0.0445 (1849/41580). AF 95% confidence interval is 0.0428. There are 94 homozygotes in gnomad4. There are 2087 alleles in male gnomad4 subpopulation. Median coverage is 34. This position pass quality control queck.

BS2

High AC in GnomAd4 at 4461 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI2	NM_001374353.1 linkuse as main transcript	c.1317+25C>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.1317+25C>T		intron_variant		1	NM_001374353.1	ENSP00000354586.5		A0A7I2PJA1

Frequencies

GnomAD3 genomes

AF:

0.0293

AC:

4456

AN:

152216

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0446

Gnomad AMI

AF:

0.00219

Gnomad AMR

AF:

0.0232

Gnomad ASJ

AF:

0.0758

Gnomad EAS

AF:

0.000386

Gnomad SAS

AF:

0.0219

Gnomad FIN

AF:

0.00349

Gnomad MID

AF:

0.0665

Gnomad NFE

AF:

0.0258

Gnomad OTH

AF:

0.0310

GnomAD3 exomes

AF:

0.0238

AC:

5931

AN:

249058

Hom.:

AF XY:

0.0238

AC XY:

3209

AN XY:

134932

show subpopulations

Gnomad AFR exome

AF:

0.0454

Gnomad AMR exome

AF:

0.0151

Gnomad ASJ exome

AF:

0.0703

Gnomad EAS exome

AF:

0.000218

Gnomad SAS exome

AF:

0.0229

Gnomad FIN exome

AF:

0.00455

Gnomad NFE exome

AF:

0.0271

Gnomad OTH exome

AF:

0.0243

GnomAD4 exome

AF:

0.0260

AC:

37890

AN:

1459566

Hom.:

567

Cov.:

AF XY:

0.0260

AC XY:

18846

AN XY:

726102

show subpopulations

Gnomad4 AFR exome

AF:

0.0436

Gnomad4 AMR exome

AF:

0.0166

Gnomad4 ASJ exome

AF:

0.0681

Gnomad4 EAS exome

AF:

0.0000756

Gnomad4 SAS exome

AF:

0.0234

Gnomad4 FIN exome

AF:

0.00558

Gnomad4 NFE exome

AF:

0.0267

Gnomad4 OTH exome

AF:

0.0296

GnomAD4 genome

AF:

0.0293

AC:

4461

AN:

152334

Hom.:

Cov.:

AF XY:

0.0280

AC XY:

2087

AN XY:

74488

show subpopulations

Gnomad4 AFR

AF:

0.0445

Gnomad4 AMR

AF:

0.0232

Gnomad4 ASJ

AF:

0.0758

Gnomad4 EAS

AF:

0.000387

Gnomad4 SAS

AF:

0.0222

Gnomad4 FIN

AF:

0.00349

Gnomad4 NFE

AF:

0.0259

Gnomad4 OTH

AF:

0.0307

Alfa

AF:

0.0319

Hom.:

Bravo

AF:

0.0306

Asia WGS

AF:

0.0150

AC:

AN:

3478

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Likely benign, criteria provided, single submitter	clinical testing	GeneDx	Jan 09, 2019	- -
Likely benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

not specified

Benign:1

Likely 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

-0.93

CADD

Benign

0.071

DANN

Benign

0.64

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