rs146811565
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1
The NM_001374353.1(GLI2):c.2889C>T(p.Ser963=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00812 in 1,490,924 control chromosomes in the GnomAD database, including 853 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).
Frequency
Genomes: 𝑓 0.044 ( 510 hom., cov: 33)
Exomes 𝑓: 0.0041 ( 343 hom. )
Consequence
GLI2
NM_001374353.1 synonymous
NM_001374353.1 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -1.78
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 (BayesDel_noAF=-0.85).
BP6
?
Variant 2-120988854-C-T is Benign according to our data. Variant chr2-120988854-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 194228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-120988854-C-T is described in Lovd as [Benign].
BP7
?
Synonymous conserved (PhyloP=-1.78 with no splicing effect.
BA1
?
GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.147 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GLI2 | NM_001374353.1 | c.2889C>T | p.Ser963= | synonymous_variant | 14/14 | ENST00000361492.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GLI2 | ENST00000361492.9 | c.2889C>T | p.Ser963= | synonymous_variant | 14/14 | 1 | NM_001374353.1 | P2 |
Frequencies
GnomAD3 genomes ? AF: 0.0435 AC: 6584AN: 151214Hom.: 510 Cov.: 33
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GnomAD3 exomes AF: 0.00561 AC: 630AN: 112308Hom.: 35 AF XY: 0.00434 AC XY: 270AN XY: 62144
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GnomAD4 exome AF: 0.00411 AC: 5509AN: 1339606Hom.: 343 Cov.: 30 AF XY: 0.00362 AC XY: 2392AN XY: 661220
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GnomAD4 genome ? AF: 0.0436 AC: 6592AN: 151318Hom.: 510 Cov.: 33 AF XY: 0.0418 AC XY: 3088AN XY: 73956
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not specified Benign:2
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Mar 18, 2016 | - - |
Benign, criteria provided, single submitter | clinical testing | Eurofins Ntd Llc (ga) | Jan 27, 2015 | - - |
Holoprosencephaly 9;C4014479:Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome Benign:1
Benign, criteria provided, single submitter | clinical testing | Invitae | Jan 25, 2024 | - - |
Holoprosencephaly 9 Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Illumina Laboratory Services, Illumina | Apr 27, 2017 | This variant was observed as part of a predisposition screen in an ostensibly healthy population. A literature search was performed for the gene, cDNA change, and amino acid change (where applicable). No publications were found based on this search. Allele frequency data from public databases allowed determination this variant is unlikely to cause disease. Therefore, this variant is classified as likely benign. - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Oct 11, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at