rs280192

Variant names:

• chr2-120979622-G-A
• rs280192
• NM_001374353.1:c.1467+1039G>A

Your query was ambiguous. Multiple possible variants found:

• chr2-120979622-G-A
• chr2-120979622-G-C
• chr2-120979622-G-T

Variant summary

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

The NM_001374353.1(GLI2):​c.1467+1039G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.663 in 151,974 control chromosomes in the GnomAD database, including 33,918 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 0.66 (33918 hom., cov: 33)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.17
• Publications: 7 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: G2P, Ambry Genetics, Labcorp Genetics (formerly Invitae)
• postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, Orphanet, Illumina
• 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=-0.91).
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.734 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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI2	NM_001374353.1	MANE Select	c.1467+1039G>A		intron	N/A	NP_001361282.1	A0A7I2PJA1
	GLI2	NM_001371271.1		c.1518+1039G>A		intron	N/A	NP_001358200.1	P10070-5
	GLI2	NM_005270.5		c.1518+1039G>A		intron	N/A	NP_005261.2	P10070-5

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GLI2	ENST00000361492.9	TSL:1 MANE Select	c.1467+1039G>A		intron	N/A	ENSP00000354586.5	A0A7I2PJA1
	GLI2	ENST00000452319.6	TSL:5	c.1518+1039G>A		intron	N/A	ENSP00000390436.1	P10070-5
	GLI2	ENST00000934404.1		c.1461+1039G>A		intron	N/A	ENSP00000604463.1

Frequencies

GnomAD3 genomes AF: 0.663 AC: 100686 AN: 151856 Hom.: 33897 Cov.: 33

Gnomad AFR AF: 0.567

Gnomad AMI AF: 0.802

Gnomad AMR AF: 0.652

Gnomad ASJ AF: 0.709

Gnomad EAS AF: 0.501

Gnomad SAS AF: 0.530

Gnomad FIN AF: 0.673

Gnomad MID AF: 0.677

Gnomad NFE AF: 0.739

Gnomad OTH AF: 0.679

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

GnomAD4 genome AF: 0.663 AC: 100742 AN: 151974 Hom.: 33918 Cov.: 33 AF XY: 0.658 AC XY: 48883 AN XY: 74288

African (AFR) AF: 0.566 AC: 23461 AN: 41418

American (AMR) AF: 0.652 AC: 9960 AN: 15282

Ashkenazi Jewish (ASJ) AF: 0.709 AC: 2461 AN: 3472

East Asian (EAS) AF: 0.501 AC: 2588 AN: 5168

South Asian (SAS) AF: 0.531 AC: 2553 AN: 4812

European-Finnish (FIN) AF: 0.673 AC: 7101 AN: 10556

Middle Eastern (MID) AF: 0.697 AC: 205 AN: 294

European-Non Finnish (NFE) AF: 0.739 AC: 50249 AN: 67952

Other (OTH) AF: 0.680 AC: 1433 AN: 2108

Alfa AF: 0.639 Hom.: 3451

Bravo AF: 0.656

Asia WGS AF: 0.544 AC: 1895 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.010
DANN	Benign	0.37
PhyloP100		-1.2
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: rs280192; hg19: chr2-121737198;