NM_001374353.1:c.-30-24516C>T

Variant names:

• chr2-120772775-C-T
• rs11677381
• NM_001374353.1:c.-30-24516C>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.-30-24516C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.066 in 152,286 control chromosomes in the GnomAD database, including 423 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 0.066 (423 hom., cov: 33)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.64
• Publications: 5 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=-0.98).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.114 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLI2	NM_001374353.1	c.-30-24516C>T		intron_variant	Intron 1 of 13	ENST00000361492.9	NP_001361282.1
GLI2	NM_001371271.1	c.-30-24516C>T		intron_variant	Intron 1 of 13		NP_001358200.1
GLI2	NM_001374354.1	c.-299-24516C>T		intron_variant	Intron 1 of 12		NP_001361283.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLI2	ENST00000361492.9	c.-30-24516C>T		intron_variant	Intron 1 of 13	1	NM_001374353.1	ENSP00000354586.5
GLI2	ENST00000482119.6	c.-30-24516C>T		intron_variant	Intron 1 of 3	2		ENSP00000502423.1
GLI2	ENST00000472722.5	n.60-24516C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0659 AC: 10030 AN: 152168 Hom.: 418 Cov.: 33

Gnomad AFR AF: 0.0439

Gnomad AMI AF: 0.172

Gnomad AMR AF: 0.118

Gnomad ASJ AF: 0.0775

Gnomad EAS AF: 0.000770

Gnomad SAS AF: 0.0696

Gnomad FIN AF: 0.0946

Gnomad MID AF: 0.0886

Gnomad NFE AF: 0.0660

Gnomad OTH AF: 0.0607

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

GnomAD4 genome AF: 0.0660 AC: 10051 AN: 152286 Hom.: 423 Cov.: 33 AF XY: 0.0660 AC XY: 4918 AN XY: 74466

African (AFR) AF: 0.0439 AC: 1825 AN: 41562

American (AMR) AF: 0.119 AC: 1818 AN: 15302

Ashkenazi Jewish (ASJ) AF: 0.0775 AC: 269 AN: 3472

East Asian (EAS) AF: 0.000772 AC: 4 AN: 5184

South Asian (SAS) AF: 0.0700 AC: 338 AN: 4826

European-Finnish (FIN) AF: 0.0946 AC: 1002 AN: 10594

Middle Eastern (MID) AF: 0.0850 AC: 25 AN: 294

European-Non Finnish (NFE) AF: 0.0659 AC: 4486 AN: 68026

Other (OTH) AF: 0.0601 AC: 127 AN: 2114

Alfa AF: 0.0639 Hom.: 678

Bravo AF: 0.0690

Asia WGS AF: 0.0320 AC: 111 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.98
CADD	Benign	0.16
DANN	Benign	0.80
PhyloP100		-2.6

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs11677381; hg19: chr2-121530351;