rs2592595
Positions:
Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001374353.1(GLI2):c.801G>A(p.Ser267=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.959 in 1,613,450 control chromosomes in the GnomAD database, including 751,378 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.84 ( 57441 hom., cov: 33)
Exomes 𝑓: 0.97 ( 693937 hom. )
Consequence
GLI2
NM_001374353.1 synonymous
NM_001374353.1 synonymous
Scores
13
Clinical Significance
Conservation
PhyloP100: -5.92
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 Benign. Variant got -21 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=7.7370595E-7).
BP6
?
Variant 2-120968871-G-A is Benign according to our data. Variant chr2-120968871-G-A is described in ClinVar as [Benign]. Clinvar id is 259736.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-120968871-G-A is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-5.92 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.979 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLI2 | NM_001374353.1 | c.801G>A | p.Ser267= | synonymous_variant | 6/14 | ENST00000361492.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLI2 | ENST00000361492.9 | c.801G>A | p.Ser267= | synonymous_variant | 6/14 | 1 | NM_001374353.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.840 AC: 127750AN: 152102Hom.: 57432 Cov.: 33
GnomAD3 genomes
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GnomAD3 exomes AF: 0.949 AC: 238228AN: 251088Hom.: 115106 AF XY: 0.959 AC XY: 130207AN XY: 135818
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GnomAD4 exome AF: 0.971 AC: 1418808AN: 1461228Hom.: 693937 Cov.: 55 AF XY: 0.973 AC XY: 707184AN XY: 726942
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GnomAD4 genome ? AF: 0.840 AC: 127800AN: 152222Hom.: 57441 Cov.: 33 AF XY: 0.845 AC XY: 62874AN XY: 74430
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ClinVar
Significance: Benign
Submissions summary: Benign:8
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Benign, no assertion criteria provided | clinical testing | Clinical Genetics, Academic Medical Center | - | - - |
Holoprosencephaly 9 Benign:2
Benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Jan 13, 2018 | This variant was observed in the ICSL laboratory as part of a predisposition screen in an ostensibly healthy population. It had not been previously curated by ICSL or reported in the Human Gene Mutation Database (HGMD: prior to June 1st, 2018), and was therefore a candidate for classification through an automated scoring system. Utilizing variant allele frequency, disease prevalence and penetrance estimates, and inheritance mode, an automated score was calculated to assess if this variant is too frequent to cause the disease. Based on the score and internal cut-off values, a variant classified as benign is not then subjected to further curation. The score for this variant resulted in a classification of benign for this disease. - |
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Holoprosencephaly 9;C4014479:Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Feb 01, 2024 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 28, 2018 | - - |
Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
Computational scores
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Name
Calibrated prediction
Score
Prediction
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
N
LIST_S2
Benign
T
MetaRNN
Benign
T
MetaSVM
Benign
T
MutationTaster
Benign
P;P;P
PROVEAN
Benign
N
REVEL
Benign
Sift
Benign
T
ClinPred
T
GERP RS
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at