2-120955465-T-C
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The ENST00000361492.9(GLI2):c.643+35T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.916 in 1,364,864 control chromosomes in the GnomAD database, including 584,437 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.79 ( 52061 hom., cov: 33)
Exomes 𝑓: 0.93 ( 532376 hom. )
Consequence
GLI2
ENST00000361492.9 intron
ENST00000361492.9 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.895
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 -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
Variant 2-120955465-T-C is Benign according to our data. Variant chr2-120955465-T-C is described in ClinVar as [Benign]. Clinvar id is 259733.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.976 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
GLI2 | NM_001374353.1 | c.643+35T>C | intron_variant | ENST00000361492.9 | NP_001361282.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
GLI2 | ENST00000361492.9 | c.643+35T>C | intron_variant | 1 | NM_001374353.1 | ENSP00000354586 | P2 |
Frequencies
GnomAD3 genomes AF: 0.788 AC: 119839AN: 152068Hom.: 52058 Cov.: 33
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GnomAD3 exomes AF: 0.913 AC: 142153AN: 155738Hom.: 66452 AF XY: 0.922 AC XY: 77584AN XY: 84144
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GnomAD4 exome AF: 0.932 AC: 1130477AN: 1212678Hom.: 532376 Cov.: 16 AF XY: 0.934 AC XY: 564548AN XY: 604172
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GnomAD4 genome AF: 0.788 AC: 119866AN: 152186Hom.: 52061 Cov.: 33 AF XY: 0.795 AC XY: 59147AN XY: 74416
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ClinVar
Significance: Benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | GeneDx | Apr 12, 2019 | - - |
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | - | - - |
Holoprosencephaly 9 Benign:1
Benign, criteria provided, single submitter | clinical testing | Genome-Nilou Lab | Aug 10, 2021 | - - |
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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BayesDel_noAF
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CADD
Benign
DANN
Benign
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