2-120837504-G-A

Position:

• chr2-120837504-G-A

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374353.1(GLI2):​c.148+40036G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.224 in 151,972 control chromosomes in the GnomAD database, including 4,774 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.22 (4774 hom., cov: 32)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.154

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.98).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.382 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI2	NM_001374353.1	c.148+40036G>A		intron_variant		ENST00000361492.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI2	ENST00000361492.9	c.148+40036G>A		intron_variant		1	NM_001374353.1	P2

Frequencies

GnomAD3 genomes AF: 0.224 AC: 34005 AN: 151856 Hom.: 4754 Cov.: 32

Gnomad AFR AF: 0.387

Gnomad AMI AF: 0.233

Gnomad AMR AF: 0.172

Gnomad ASJ AF: 0.346

Gnomad EAS AF: 0.00212

Gnomad SAS AF: 0.0875

Gnomad FIN AF: 0.157

Gnomad MID AF: 0.285

Gnomad NFE AF: 0.167

Gnomad OTH AF: 0.234

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.224 AC: 34062 AN: 151972 Hom.: 4774 Cov.: 32 AF XY: 0.222 AC XY: 16455 AN XY: 74288

Gnomad4 AFR AF: 0.387

Gnomad4 AMR AF: 0.171

Gnomad4 ASJ AF: 0.346

Gnomad4 EAS AF: 0.00212

Gnomad4 SAS AF: 0.0876

Gnomad4 FIN AF: 0.157

Gnomad4 NFE AF: 0.167

Gnomad4 OTH AF: 0.230

Alfa AF: 0.187 Hom.: 1765

Bravo AF: 0.236

Asia WGS AF: 0.0690 AC: 238 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	4.0
DANN	Benign	0.82

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

Other links and lift over

dbSNP: rs2310897; hg19: chr2-121595079;