2-120797328-C-T
Variant summary
Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_ModerateBS2
The NM_001374354.1(GLI2):c.-262C>T variant causes a 5 prime UTR premature start codon gain change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000297 in 1,613,806 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★).
Frequency
Consequence
NM_001374354.1 5_prime_UTR_premature_start_codon_gain
Scores
Clinical Significance
Conservation
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ACMG classification
Verdict is Likely_benign. Variant got -6 ACMG points.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLI2 | NM_001374353.1 | c.8C>T | p.Thr3Met | missense_variant | Exon 2 of 14 | ENST00000361492.9 | NP_001361282.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | Exon rank | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLI2 | ENST00000361492.9 | c.8C>T | p.Thr3Met | missense_variant | Exon 2 of 14 | 1 | NM_001374353.1 | ENSP00000354586.5 |
Frequencies
GnomAD3 genomes AF: 0.0000460 AC: 7AN: 152068Hom.: 0 Cov.: 32
GnomAD3 exomes AF: 0.0000318 AC: 8AN: 251220Hom.: 0 AF XY: 0.0000221 AC XY: 3AN XY: 135876
GnomAD4 exome AF: 0.0000280 AC: 41AN: 1461738Hom.: 0 Cov.: 31 AF XY: 0.0000303 AC XY: 22AN XY: 727184
GnomAD4 genome AF: 0.0000460 AC: 7AN: 152068Hom.: 0 Cov.: 32 AF XY: 0.0000404 AC XY: 3AN XY: 74270
ClinVar
Submissions by phenotype
Inborn genetic diseases Uncertain:1
The c.8C>T (p.T3M) alteration is located in exon 1 (coding exon 1) of the GLI2 gene. This alteration results from a C to T substitution at nucleotide position 8, causing the threonine (T) at amino acid position 3 to be replaced by a methionine (M). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -
Holoprosencephaly 9;C4014479:Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome Uncertain:1
This variant is present in population databases (rs770918439, gnomAD 0.01%). This sequence change replaces threonine, which is neutral and polar, with methionine, which is neutral and non-polar, at codon 3 of the GLI2 protein (p.Thr3Met). This variant has not been reported in the literature in individuals affected with GLI2-related conditions. ClinVar contains an entry for this variant (Variation ID: 1354011). Algorithms developed to predict the effect of missense changes on protein structure and function output the following: SIFT: "Deleterious"; PolyPhen-2: "Benign"; Align-GVGD: "Class C0". The methionine amino acid residue is found in multiple mammalian species, which suggests that this missense change does not adversely affect protein function. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance. -
Computational scores
Source:
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at