2-120783436-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.-30-13855C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 152,092 control chromosomes in the GnomAD database, including 406 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 0.064 (406 hom., cov: 32)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733

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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GLI2	NM_001374353.1	c.-30-13855C>T		intron_variant		ENST00000361492.9
GLI2	NM_001371271.1	c.-30-13855C>T		intron_variant
GLI2	NM_001374354.1	c.-299-13855C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI2	ENST00000361492.9	c.-30-13855C>T		intron_variant		1	NM_001374353.1	P2
GLI2	ENST00000482119.6	c.-30-13855C>T		intron_variant		2
GLI2	ENST00000472722.5	n.60-13855C>T		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9738 AN: 151974 Hom.: 401 Cov.: 32

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0587

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

GnomAD4 genome AF: 0.0642 AC: 9759 AN: 152092 Hom.: 406 Cov.: 32 AF XY: 0.0641 AC XY: 4764 AN XY: 74338

Gnomad4 AFR AF: 0.0436

Gnomad4 AMR AF: 0.115

Gnomad4 ASJ AF: 0.0723

Gnomad4 EAS AF: 0.000970

Gnomad4 SAS AF: 0.0660

Gnomad4 FIN AF: 0.0917

Gnomad4 NFE AF: 0.0639

Gnomad4 OTH AF: 0.0581

Alfa AF: 0.0328 Hom.: 19

Bravo AF: 0.0677

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
Cadd	Benign	1.3
Dann	Benign	0.82

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs11685068; hg19: chr2-121541012;