chr2-120797391-G-A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001374353.1(GLI2):​c.71G>A​(p.Gly24Asp) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 32)

Consequence

GLI2
NM_001374353.1 missense

Scores

3
16

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.39
Variant links:
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19883785).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GLI2NM_001374353.1 linkuse as main transcriptc.71G>A p.Gly24Asp missense_variant 2/14 ENST00000361492.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GLI2ENST00000361492.9 linkuse as main transcriptc.71G>A p.Gly24Asp missense_variant 2/141 NM_001374353.1 P2

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
Cov.:
31
GnomAD4 genome
Cov.:
32

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not provided Uncertain:1
Uncertain significance, criteria provided, single submitterclinical testingRevvity Omics, RevvityNov 10, 2023- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.17
BayesDel_addAF
Benign
-0.15
T
BayesDel_noAF
Benign
-0.45
CADD
Benign
15
DANN
Benign
0.84
DEOGEN2
Benign
0.33
T;T;T;.
Eigen
Benign
-0.21
Eigen_PC
Benign
-0.23
FATHMM_MKL
Uncertain
0.77
D
LIST_S2
Benign
0.58
T;.;T;T
M_CAP
Benign
0.0081
T
MetaRNN
Benign
0.20
T;T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.5
.;L;L;.
MutationTaster
Benign
1.0
D;N;N
PrimateAI
Benign
0.37
T
PROVEAN
Uncertain
-2.4
N;N;N;N
REVEL
Benign
0.11
Sift
Benign
0.032
D;D;D;D
Sift4G
Uncertain
0.035
D;T;T;D
Polyphen
0.88
.;P;P;.
Vest4
0.22, 0.22
MutPred
0.094
Loss of catalytic residue at A23 (P = 0.1134);Loss of catalytic residue at A23 (P = 0.1134);Loss of catalytic residue at A23 (P = 0.1134);.;
MVP
0.42
MPC
0.47
ClinPred
0.52
D
GERP RS
3.0
Varity_R
0.11
gMVP
0.24

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.050
Details are displayed if max score is > 0.2

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

Publications

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-121554967; API