rs7569576

Variant names:

• chr2-120797174-A-G
• rs7569576
• NM_001374353.1:c.-30-117A>G

Your query was ambiguous. Multiple possible variants found:

• chr2-120797174-A-G
• chr2-120797174-A-T

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001374353.1(GLI2):​c.-30-117A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0145 in 762,050 control chromosomes in the GnomAD database, including 860 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.048 (605 hom., cov: 32)
  • Exomes 𝑓: 0.0061 (255 hom.)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -0.856
• Publications: 2 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, Labcorp Genetics (formerly Invitae), Ambry Genetics
• postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome

  Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, 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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BP6: Variant 2-120797174-A-G is Benign according to our data. Variant chr2-120797174-A-G is described in ClinVar as Benign. ClinVar VariationId is 1267464.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.161 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.-30-117A>G		intron	N/A	NP_001361282.1	A0A7I2PJA1
	GLI2	NM_001371271.1		c.-30-117A>G		intron	N/A	NP_001358200.1	P10070-5
	GLI2	NM_005270.5		c.-30-117A>G		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.-30-117A>G		intron	N/A	ENSP00000354586.5	A0A7I2PJA1
	GLI2	ENST00000418323.6	TSL:1	c.-30-117A>G		intron	N/A	ENSP00000398992.1	Q1PSW9
	GLI2	ENST00000934404.1		c.-30-117A>G		intron	N/A	ENSP00000604463.1

Frequencies

GnomAD3 genomes AF: 0.0478 AC: 7264 AN: 152112 Hom.: 601 Cov.: 32

Gnomad AFR AF: 0.164

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0219

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00104

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00316

Gnomad NFE AF: 0.000809

Gnomad OTH AF: 0.0306

GnomAD4 exome AF: 0.00612 AC: 3730 AN: 609820 Hom.: 255 AF XY: 0.00500 AC XY: 1636 AN XY: 327020

African (AFR) AF: 0.167 AC: 2666 AN: 15968

American (AMR) AF: 0.0112 AC: 378 AN: 33894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 19040

East Asian (EAS) AF: 0.0000282 AC: 1 AN: 35422

South Asian (SAS) AF: 0.000566 AC: 36 AN: 63598

European-Finnish (FIN) AF: 0.0000221 AC: 1 AN: 45172

Middle Eastern (MID) AF: 0.00683 AC: 26 AN: 3804

European-Non Finnish (NFE) AF: 0.000565 AC: 204 AN: 361198

Other (OTH) AF: 0.0132 AC: 418 AN: 31724

GnomAD4 genome AF: 0.0478 AC: 7283 AN: 152230 Hom.: 605 Cov.: 32 AF XY: 0.0462 AC XY: 3439 AN XY: 74436

African (AFR) AF: 0.164 AC: 6824 AN: 41510

American (AMR) AF: 0.0219 AC: 335 AN: 15304

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5174

South Asian (SAS) AF: 0.00104 AC: 5 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00340 AC: 1 AN: 294

European-Non Finnish (NFE) AF: 0.000794 AC: 54 AN: 68014

Other (OTH) AF: 0.0303 AC: 64 AN: 2112

Alfa AF: 0.0274 Hom.: 119

Bravo AF: 0.0540

Asia WGS AF: 0.0100 AC: 36 AN: 3478

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	2	not provided (2)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	8.2
DANN	Benign	0.48
PhyloP100		-0.86
PromoterAI		-0.018	Neutral
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: rs7569576; hg19: chr2-121554750;