rs17005499

Variant names:

• chr2-120951865-G-A
• rs17005499
• NM_001374353.1:c.457+420G>A

Variant summary

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

The NM_001374353.1(GLI2):​c.457+420G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0978 in 158,576 control chromosomes in the GnomAD database, including 2,505 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 0.10 (2486 hom., cov: 33)
  • Exomes 𝑓: 0.021 (19 hom.)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.473

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 = 0.34 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLI2	NM_001374353.1	c.457+420G>A		intron_variant	Intron 4 of 13	ENST00000361492.9	NP_001361282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLI2	ENST00000361492.9	c.457+420G>A		intron_variant	Intron 4 of 13	1	NM_001374353.1	ENSP00000354586.5

Frequencies

GnomAD3 genomes AF: 0.101 AC: 15330 AN: 152002 Hom.: 2480 Cov.: 33

Gnomad AFR AF: 0.345

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0196

Gnomad EAS AF: 0.000194

Gnomad SAS AF: 0.0118

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.0253

Gnomad NFE AF: 0.00247

Gnomad OTH AF: 0.0651

GnomAD4 exome AF: 0.0208 AC: 134 AN: 6456 Hom.: 19 AF XY: 0.0184 AC XY: 61 AN XY: 3308

Gnomad4 AFR exome AF: 0.312

Gnomad4 AMR exome AF: 0.0294

Gnomad4 ASJ exome AF: 0.0111

Gnomad4 EAS exome AF: 0.00

Gnomad4 SAS exome AF: 0.0385

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00349

Gnomad4 OTH exome AF: 0.0498

GnomAD4 genome AF: 0.101 AC: 15372 AN: 152120 Hom.: 2486 Cov.: 33 AF XY: 0.0976 AC XY: 7257 AN XY: 74386

Gnomad4 AFR AF: 0.345

Gnomad4 AMR AF: 0.0422

Gnomad4 ASJ AF: 0.0196

Gnomad4 EAS AF: 0.000194

Gnomad4 SAS AF: 0.0118

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00248

Gnomad4 OTH AF: 0.0645

Alfa AF: 0.0855 Hom.: 234

Bravo AF: 0.116

Asia WGS AF: 0.0250 AC: 87 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	0.61
DANN	Benign	0.45

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: rs17005499; hg19: chr2-121709441;