rs4848632

Positions:

• chr2-120805019-A-G

Variant summary

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

The NM_001374353.1(GLI2):​c.148+7551A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,124 control chromosomes in the GnomAD database, including 22,383 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 0.52 (22383 hom., cov: 33)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670

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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI2	NM_001374353.1	c.148+7551A>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.148+7551A>G		intron_variant		1	NM_001374353.1	ENSP00000354586	P2

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78791 AN: 152006 Hom.: 22382 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.518 AC: 78807 AN: 152124 Hom.: 22383 Cov.: 33 AF XY: 0.524 AC XY: 38947 AN XY: 74354

Gnomad4 AFR AF: 0.267

Gnomad4 AMR AF: 0.573

Gnomad4 ASJ AF: 0.504

Gnomad4 EAS AF: 0.686

Gnomad4 SAS AF: 0.697

Gnomad4 FIN AF: 0.640

Gnomad4 NFE AF: 0.611

Gnomad4 OTH AF: 0.537

Alfa AF: 0.594 Hom.: 46822

Bravo AF: 0.498

Asia WGS AF: 0.668 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.20

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: rs4848632; hg19: chr2-121562595;