chr2-120979622-G-A

Position:

• chr2-120979622-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.1467+1039G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 151,974 control chromosomes in the GnomAD database, including 33,918 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 0.66 (33918 hom., cov: 33)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17

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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI2	NM_001374353.1	c.1467+1039G>A		intron_variant		ENST00000361492.9	NP_001361282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI2	ENST00000361492.9	c.1467+1039G>A		intron_variant		1	NM_001374353.1	ENSP00000354586.5

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100686 AN: 151856 Hom.: 33897 Cov.: 33

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.663 AC: 100742 AN: 151974 Hom.: 33918 Cov.: 33 AF XY: 0.658 AC XY: 48883 AN XY: 74288

Gnomad4 AFR AF: 0.566

Gnomad4 AMR AF: 0.652

Gnomad4 ASJ AF: 0.709

Gnomad4 EAS AF: 0.501

Gnomad4 SAS AF: 0.531

Gnomad4 FIN AF: 0.673

Gnomad4 NFE AF: 0.739

Gnomad4 OTH AF: 0.680

Alfa AF: 0.639 Hom.: 3451

Bravo AF: 0.656

Asia WGS AF: 0.544 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.010
DANN	Benign	0.37

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: rs280192; hg19: chr2-121737198;