chr2-120805019-A-G

Variant names:

• chr2-120805019-A-G
• rs4848632
• NM_001374353.1:c.148+7551A>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.148+7551A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.518 in 152,124 control chromosomes in the GnomAD database, including 22,383 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 0.52 (22383 hom., cov: 33)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.670
• Publications: 9 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=-0.93).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.677 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.148+7551A>G		intron	N/A	NP_001361282.1
	GLI2	NM_001371271.1		c.148+7551A>G		intron	N/A	NP_001358200.1
	GLI2	NM_005270.5		c.148+7551A>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.148+7551A>G		intron	N/A	ENSP00000354586.5
	GLI2	ENST00000418323.6	TSL:1	c.148+7551A>G		intron	N/A	ENSP00000398992.1
	GLI2	ENST00000360874.10	TSL:1	n.124+7551A>G		intron	N/A

Frequencies

GnomAD3 genomes AF: 0.518 AC: 78791 AN: 152006 Hom.: 22382 Cov.: 33

Gnomad AFR AF: 0.267

Gnomad AMI AF: 0.746

Gnomad AMR AF: 0.573

Gnomad ASJ AF: 0.504

Gnomad EAS AF: 0.687

Gnomad SAS AF: 0.696

Gnomad FIN AF: 0.640

Gnomad MID AF: 0.576

Gnomad NFE AF: 0.611

Gnomad OTH AF: 0.535

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

GnomAD4 genome AF: 0.518 AC: 78807 AN: 152124 Hom.: 22383 Cov.: 33 AF XY: 0.524 AC XY: 38947 AN XY: 74354

African (AFR) AF: 0.267 AC: 11085 AN: 41500

American (AMR) AF: 0.573 AC: 8760 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.504 AC: 1747 AN: 3466

East Asian (EAS) AF: 0.686 AC: 3540 AN: 5162

South Asian (SAS) AF: 0.697 AC: 3360 AN: 4824

European-Finnish (FIN) AF: 0.640 AC: 6768 AN: 10574

Middle Eastern (MID) AF: 0.582 AC: 171 AN: 294

European-Non Finnish (NFE) AF: 0.611 AC: 41564 AN: 67996

Other (OTH) AF: 0.537 AC: 1132 AN: 2108

Alfa AF: 0.581 Hom.: 103312

Bravo AF: 0.498

Asia WGS AF: 0.668 AC: 2321 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.93
CADD	Benign	1.1
DANN	Benign	0.20
PhyloP100		-0.67
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: rs4848632; hg19: chr2-121562595;