rs1992901

Positions:

• chr2-120913093-A-G
• chr2-120913093-A-T

Variant summary

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

The NM_001374353.1(GLI2):​c.149-14268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,118 control chromosomes in the GnomAD database, including 29,414 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 0.62 (29414 hom., cov: 33)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940

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=-0.9).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.637 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI2	NM_001374353.1	c.149-14268A>G		intron_variant		ENST00000361492.9	NP_001361282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI2	ENST00000361492.9	c.149-14268A>G		intron_variant		1	NM_001374353.1	ENSP00000354586	P2

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94404 AN: 152000 Hom.: 29388 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.621 AC: 94480 AN: 152118 Hom.: 29414 Cov.: 33 AF XY: 0.619 AC XY: 46058 AN XY: 74370

Gnomad4 AFR AF: 0.644

Gnomad4 AMR AF: 0.570

Gnomad4 ASJ AF: 0.671

Gnomad4 EAS AF: 0.469

Gnomad4 SAS AF: 0.625

Gnomad4 FIN AF: 0.603

Gnomad4 NFE AF: 0.629

Gnomad4 OTH AF: 0.625

Alfa AF: 0.629 Hom.: 45616

Bravo AF: 0.617

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
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: rs1992901; hg19: chr2-121670669;