2-120893881-C-T

Position:

• chr2-120893881-C-T

Variant summary

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

The NM_001374353.1(GLI2):​c.149-33480C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.749 in 152,044 control chromosomes in the GnomAD database, including 43,067 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 0.75 (43067 hom., cov: 31)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 2.72

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=-0.55).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.9 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI2	NM_001374353.1	c.149-33480C>T		intron_variant		ENST00000361492.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI2	ENST00000361492.9	c.149-33480C>T		intron_variant		1	NM_001374353.1	P2

Frequencies

GnomAD3 genomes AF: 0.749 AC: 113844 AN: 151926 Hom.: 43076 Cov.: 31

Gnomad AFR AF: 0.652

Gnomad AMI AF: 0.941

Gnomad AMR AF: 0.738

Gnomad ASJ AF: 0.802

Gnomad EAS AF: 0.922

Gnomad SAS AF: 0.864

Gnomad FIN AF: 0.753

Gnomad MID AF: 0.797

Gnomad NFE AF: 0.783

Gnomad OTH AF: 0.777

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

GnomAD4 genome AF: 0.749 AC: 113866 AN: 152044 Hom.: 43067 Cov.: 31 AF XY: 0.749 AC XY: 55647 AN XY: 74322

Gnomad4 AFR AF: 0.651

Gnomad4 AMR AF: 0.737

Gnomad4 ASJ AF: 0.802

Gnomad4 EAS AF: 0.922

Gnomad4 SAS AF: 0.863

Gnomad4 FIN AF: 0.753

Gnomad4 NFE AF: 0.783

Gnomad4 OTH AF: 0.773

Alfa AF: 0.782 Hom.: 65341

Bravo AF: 0.744

Asia WGS AF: 0.866 AC: 3013 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	20
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

Other links and lift over

dbSNP: rs277534; hg19: chr2-121651457;