2-120783436-C-T

Variant names:

• chr2-120783436-C-T
• rs11685068
• NM_001374353.1:c.-30-13855C>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.-30-13855C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0642 in 152,092 control chromosomes in the GnomAD database, including 406 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 0.064 (406 hom., cov: 32)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.733
• Publications: 8 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=-0.81).
• BA1: GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.11 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLI2	NM_001374353.1	c.-30-13855C>T		intron_variant	Intron 1 of 13	ENST00000361492.9	NP_001361282.1
GLI2	NM_001371271.1	c.-30-13855C>T		intron_variant	Intron 1 of 13		NP_001358200.1
GLI2	NM_001374354.1	c.-299-13855C>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.-30-13855C>T		intron_variant	Intron 1 of 13	1	NM_001374353.1	ENSP00000354586.5
GLI2	ENST00000482119.6	c.-30-13855C>T		intron_variant	Intron 1 of 3	2		ENSP00000502423.1
GLI2	ENST00000472722.5	n.60-13855C>T		intron_variant	Intron 1 of 3	2

Frequencies

GnomAD3 genomes AF: 0.0641 AC: 9738 AN: 151974 Hom.: 401 Cov.: 32

Gnomad AFR AF: 0.0436

Gnomad AMI AF: 0.174

Gnomad AMR AF: 0.114

Gnomad ASJ AF: 0.0723

Gnomad EAS AF: 0.000967

Gnomad SAS AF: 0.0657

Gnomad FIN AF: 0.0917

Gnomad MID AF: 0.0918

Gnomad NFE AF: 0.0639

Gnomad OTH AF: 0.0587

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

GnomAD4 genome AF: 0.0642 AC: 9759 AN: 152092 Hom.: 406 Cov.: 32 AF XY: 0.0641 AC XY: 4764 AN XY: 74338

African (AFR) AF: 0.0436 AC: 1809 AN: 41484

American (AMR) AF: 0.115 AC: 1756 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.0723 AC: 251 AN: 3470

East Asian (EAS) AF: 0.000970 AC: 5 AN: 5156

South Asian (SAS) AF: 0.0660 AC: 317 AN: 4804

European-Finnish (FIN) AF: 0.0917 AC: 972 AN: 10598

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0639 AC: 4342 AN: 67986

Other (OTH) AF: 0.0581 AC: 123 AN: 2116

Alfa AF: 0.0410 Hom.: 40

Bravo AF: 0.0677

Asia WGS AF: 0.0300 AC: 105 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.81
CADD	Benign	1.3
DANN	Benign	0.82
PhyloP100		-0.73

Splicing

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

Other links and lift over

dbSNP: rs11685068; hg19: chr2-121541012;