rs12614482

chr2-120955454-G-Achr2-120955454-G-Cchr2-120955454-G-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001374353.1(GLI2):c.643+24G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.918 in 1,495,488 control chromosomes in the GnomAD database, including 642,611 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.79 (52062 hom., cov: 33)
  • Exomes 𝑓: 0.93 (590549 hom.)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:4
• Conservation: PhyloP100: 0.372

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]

ACMG classification

Verdict is Benign. Variant got -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BP6: Variant 2-120955454-G-A is Benign according to our data. Variant chr2-120955454-G-A is described in ClinVar as [Benign]. Clinvar id is 259732.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	UniProt
GLI2	NM_001374353.1	c.643+24G>A		intron_variant		ENST00000361492.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GLI2	ENST00000361492.9	c.643+24G>A		intron_variant		1	NM_001374353.1	P2

Frequencies

GnomAD3 genomes AF: 0.788 AC: 119845 AN: 152094 Hom.: 52059 Cov.: 33

Gnomad AFR AF: 0.380

Gnomad AMI AF: 0.995

Gnomad AMR AF: 0.886

Gnomad ASJ AF: 0.886

Gnomad EAS AF: 0.999

Gnomad SAS AF: 0.956

Gnomad FIN AF: 0.979

Gnomad MID AF: 0.867

Gnomad NFE AF: 0.947

Gnomad OTH AF: 0.840

GnomAD3 exomes AF: 0.916 AC: 166619 AN: 181970 Hom.: 78077 AF XY: 0.925 AC XY: 91459 AN XY: 98868

Gnomad AFR exome AF: 0.372

Gnomad AMR exome AF: 0.937

Gnomad ASJ exome AF: 0.885

Gnomad EAS exome AF: 1.00

Gnomad SAS exome AF: 0.954

Gnomad FIN exome AF: 0.974

Gnomad NFE exome AF: 0.948

Gnomad OTH exome AF: 0.922

GnomAD4 exome AF: 0.933 AC: 1253332 AN: 1343276 Hom.: 590549 Cov.: 20 AF XY: 0.935 AC XY: 623114 AN XY: 666244

Gnomad4 AFR exome AF: 0.350

Gnomad4 AMR exome AF: 0.930

Gnomad4 ASJ exome AF: 0.890

Gnomad4 EAS exome AF: 1.00

Gnomad4 SAS exome AF: 0.954

Gnomad4 FIN exome AF: 0.974

Gnomad4 NFE exome AF: 0.947

Gnomad4 OTH exome AF: 0.905

GnomAD4 genome AF: 0.788 AC: 119872 AN: 152212 Hom.: 52062 Cov.: 33 AF XY: 0.795 AC XY: 59148 AN XY: 74424

Gnomad4 AFR AF: 0.380

Gnomad4 AMR AF: 0.886

Gnomad4 ASJ AF: 0.886

Gnomad4 EAS AF: 0.999

Gnomad4 SAS AF: 0.957

Gnomad4 FIN AF: 0.979

Gnomad4 NFE AF: 0.946

Gnomad4 OTH AF: 0.841

Alfa AF: 0.862 Hom.: 11270

Bravo AF: 0.762

Asia WGS AF: 0.933 AC: 3243 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

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

- -

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 12, 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

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
Cadd	Benign	5.1
Dann	Benign	0.50

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs12614482; hg19: chr2-121713030;