chr2-120984731-C-T

Position:

chr2-120984731-C-T

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_001374353.1(GLI2):c.1893C>T(p.Thr631Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0261 in 1,612,710 control chromosomes in the GnomAD database, including 694 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.020 ( 54 hom., cov: 33)

Exomes 𝑓: 0.027 ( 640 hom. )

Consequence

GLI2
NM_001374353.1 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:6

Conservation

PhyloP100: -4.14

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=-0.53).

BP6

Variant 2-120984731-C-T is Benign according to our data. Variant chr2-120984731-C-T is described in ClinVar as [Benign]. Clinvar id is 259721.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-120984731-C-T is described in Lovd as [Benign]. Variant chr2-120984731-C-T is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-4.14 with no splicing effect.

BS1

Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.0203 (3086/152322) while in subpopulation NFE AF= 0.0292 (1989/68010). AF 95% confidence interval is 0.0282. There are 54 homozygotes in gnomad4. There are 1591 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High AC in GnomAd4 at 3086 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI2	NM_001374353.1 linkuse as main transcript	c.1893C>T	p.Thr631Thr	synonymous_variant	12/14	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.1893C>T	p.Thr631Thr	synonymous_variant	12/14	1	NM_001374353.1	ENSP00000354586.5		A0A7I2PJA1

Frequencies

GnomAD3 genomes

AF:

0.0203

AC:

3086

AN:

152204

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00506

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0157

Gnomad ASJ

AF:

0.0141

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00331

Gnomad FIN

AF:

0.0500

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0292

Gnomad OTH

AF:

0.0210

GnomAD3 exomes

AF:

0.0235

AC:

5737

AN:

244588

Hom.:

111

AF XY:

0.0233

AC XY:

3112

AN XY:

133480

show subpopulations

Gnomad AFR exome

AF:

0.00461

Gnomad AMR exome

AF:

0.0104

Gnomad ASJ exome

AF:

0.0184

Gnomad EAS exome

AF:

0.000110

Gnomad SAS exome

AF:

0.00420

Gnomad FIN exome

AF:

0.0536

Gnomad NFE exome

AF:

0.0338

Gnomad OTH exome

AF:

0.0288

GnomAD4 exome

AF:

0.0267

AC:

39044

AN:

1460388

Hom.:

640

Cov.:

AF XY:

0.0262

AC XY:

19043

AN XY:

726560

show subpopulations

Gnomad4 AFR exome

AF:

0.00445

Gnomad4 AMR exome

AF:

0.0102

Gnomad4 ASJ exome

AF:

0.0178

Gnomad4 EAS exome

AF:

0.0000504

Gnomad4 SAS exome

AF:

0.00400

Gnomad4 FIN exome

AF:

0.0562

Gnomad4 NFE exome

AF:

0.0299

Gnomad4 OTH exome

AF:

0.0224

GnomAD4 genome

AF:

0.0203

AC:

3086

AN:

152322

Hom.:

Cov.:

AF XY:

0.0214

AC XY:

1591

AN XY:

74486

show subpopulations

Gnomad4 AFR

AF:

0.00505

Gnomad4 AMR

AF:

0.0157

Gnomad4 ASJ

AF:

0.0141

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00331

Gnomad4 FIN

AF:

0.0500

Gnomad4 NFE

AF:

0.0292

Gnomad4 OTH

AF:

0.0208

Alfa

AF:

0.0224

Hom.:

Bravo

AF:

0.0167

Asia WGS

AF:

0.00260

AC:

AN:

3478

EpiCase

AF:

0.0274

EpiControl

AF:

0.0292

ClinVar

Significance: Benign

Submissions summary: Benign:6

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Benign, criteria provided, single submitter	clinical testing	GeneDx	Aug 14, 2019	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	ARUP Laboratories, Molecular Genetics and Genomics, ARUP Laboratories	Sep 08, 2023	- -

not specified

Benign:1

Benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Mar 18, 2016

- -

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

Jan 29, 2024

- -

Holoprosencephaly 9

Benign:1

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. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.53

CADD

Benign

1.4

DANN

Benign

0.77

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