chr2-120772775-C-T

Position:

• chr2-120772775-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.-30-24516C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 152,286 control chromosomes in the GnomAD database, including 423 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 0.066 (423 hom., cov: 33)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64

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]

GLI2 (HGNC:):

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 (AMR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GLI2	NM_001374353.1	c.-30-24516C>T		intron_variant		ENST00000361492.9	NP_001361282.1
GLI2	NM_001371271.1	c.-30-24516C>T		intron_variant			NP_001358200.1
GLI2	NM_001374354.1	c.-299-24516C>T		intron_variant			NP_001361283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GLI2	ENST00000361492.9	c.-30-24516C>T		intron_variant		1	NM_001374353.1	ENSP00000354586.5
GLI2	ENST00000482119.6	c.-30-24516C>T		intron_variant		2		ENSP00000502423.1
GLI2	ENST00000472722.5	n.60-24516C>T		intron_variant		2

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10030 AN: 152168 Hom.: 418 Cov.: 33

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0946

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.0607

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

GnomAD4 genome AF: 0.0660 AC: 10051 AN: 152286 Hom.: 423 Cov.: 33 AF XY: 0.0660 AC XY: 4918 AN XY: 74466

Gnomad4 AFR AF: 0.0439

Gnomad4 AMR AF: 0.119

Gnomad4 ASJ AF: 0.0775

Gnomad4 EAS AF: 0.000772

Gnomad4 SAS AF: 0.0700

Gnomad4 FIN AF: 0.0946

Gnomad4 NFE AF: 0.0659

Gnomad4 OTH AF: 0.0601

Alfa AF: 0.0623 Hom.: 487

Bravo AF: 0.0690

Asia WGS AF: 0.0320 AC: 111 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	0.16
DANN	Benign	0.80

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs11677381; hg19: chr2-121530351;