2-120913093-A-G

Variant names:

• chr2-120913093-A-G
• rs1992901
• NM_001374353.1:c.149-14268A>G

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001374353.1(GLI2):​c.149-14268A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.621 in 152,118 control chromosomes in the GnomAD database, including 29,414 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 0.62 (29414 hom., cov: 33)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.0940
• Publications: 16 publications found

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 Gene-Disease associations (from GenCC):

• holoprosencephaly 9

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), G2P
• postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Illumina, Ambry Genetics
• combined pituitary hormone deficiencies, genetic form

  Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
• holoprosencephaly

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -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 = 0.637 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374353.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI2	NM_001374353.1	MANE Select	c.149-14268A>G		intron	N/A	NP_001361282.1
	GLI2	NM_001371271.1		c.149-14268A>G		intron	N/A	NP_001358200.1
	GLI2	NM_005270.5		c.149-14268A>G		intron	N/A	NP_005261.2

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI2	ENST00000361492.9	TSL:1 MANE Select	c.149-14268A>G		intron	N/A	ENSP00000354586.5
	GLI2	ENST00000418323.6	TSL:1	c.149-14268A>G		intron	N/A	ENSP00000398992.1
	GLI2	ENST00000360874.10	TSL:1	n.125-14268A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.621 AC: 94404 AN: 152000 Hom.: 29388 Cov.: 33

Gnomad AFR AF: 0.644

Gnomad AMI AF: 0.674

Gnomad AMR AF: 0.570

Gnomad ASJ AF: 0.671

Gnomad EAS AF: 0.470

Gnomad SAS AF: 0.626

Gnomad FIN AF: 0.603

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.629

Gnomad OTH AF: 0.628

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

GnomAD4 genome AF: 0.621 AC: 94480 AN: 152118 Hom.: 29414 Cov.: 33 AF XY: 0.619 AC XY: 46058 AN XY: 74370

African (AFR) AF: 0.644 AC: 26714 AN: 41486

American (AMR) AF: 0.570 AC: 8727 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.671 AC: 2331 AN: 3472

East Asian (EAS) AF: 0.469 AC: 2422 AN: 5164

South Asian (SAS) AF: 0.625 AC: 3009 AN: 4814

European-Finnish (FIN) AF: 0.603 AC: 6388 AN: 10588

Middle Eastern (MID) AF: 0.667 AC: 196 AN: 294

European-Non Finnish (NFE) AF: 0.629 AC: 42765 AN: 67984

Other (OTH) AF: 0.625 AC: 1313 AN: 2102

Alfa AF: 0.625 Hom.: 105986

Bravo AF: 0.617

Asia WGS AF: 0.542 AC: 1884 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.90
CADD	Benign	4.8
DANN	Benign	0.82
PhyloP100		0.094
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs1992901; hg19: chr2-121670669;