chr2-120972110-T-C

Variant names:

• chr2-120972110-T-C
• rs2592590
• NM_001374353.1:c.1182+47T>C

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The NM_001374353.1(GLI2):​c.1182+47T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.969 in 1,609,734 control chromosomes in the GnomAD database, including 759,587 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.89 (61867 hom., cov: 35)
  • Exomes 𝑓: 0.98 (697720 hom.)
• Consequence: GLI2 NM_001374353.1 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -1.55

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

Our verdict: Benign. The variant received -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.94).
• BP6: Variant 2-120972110-T-C is Benign according to our data. Variant chr2-120972110-T-C is described in ClinVar as [Benign]. Clinvar id is 259710.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.98 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GLI2	NM_001374353.1	c.1182+47T>C		intron_variant	Intron 8 of 13	ENST00000361492.9	NP_001361282.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GLI2	ENST00000361492.9	c.1182+47T>C		intron_variant	Intron 8 of 13	1	NM_001374353.1	ENSP00000354586.5

Frequencies

GnomAD3 genomes AF: 0.890 AC: 135379 AN: 152156 Hom.: 61849 Cov.: 35

Gnomad AFR AF: 0.650

Gnomad AMI AF: 0.997

Gnomad AMR AF: 0.942

Gnomad ASJ AF: 0.966

Gnomad EAS AF: 1.00

Gnomad SAS AF: 0.981

Gnomad FIN AF: 0.996

Gnomad MID AF: 0.943

Gnomad NFE AF: 0.986

Gnomad OTH AF: 0.918

GnomAD2 exomes AF: 0.962 AC: 237340 AN: 246640 AF XY: 0.968

Gnomad AFR exome AF: 0.638

Gnomad AMR exome AF: 0.972

Gnomad ASJ exome AF: 0.969

Gnomad EAS exome AF: 1.00

Gnomad FIN exome AF: 0.995

Gnomad NFE exome AF: 0.987

Gnomad OTH exome AF: 0.967

GnomAD4 exome AF: 0.977 AC: 1423825 AN: 1457460 Hom.: 697720 Cov.: 32 AF XY: 0.978 AC XY: 709225 AN XY: 725214

Gnomad4 AFR exome AF: 0.631 AC: 21069 AN: 33376

Gnomad4 AMR exome AF: 0.969 AC: 43276 AN: 44664

Gnomad4 ASJ exome AF: 0.969 AC: 25264 AN: 26084

Gnomad4 EAS exome AF: 1.00 AC: 39656 AN: 39660

Gnomad4 SAS exome AF: 0.979 AC: 83996 AN: 85816

Gnomad4 FIN exome AF: 0.995 AC: 52054 AN: 52326

Gnomad4 NFE exome AF: 0.987 AC: 1095792 AN: 1110272

Gnomad4 Remaining exome AF: 0.962 AC: 57879 AN: 60190

GnomAD4 genome AF: 0.889 AC: 135445 AN: 152274 Hom.: 61867 Cov.: 35 AF XY: 0.893 AC XY: 66448 AN XY: 74450

Gnomad4 AFR AF: 0.650 AC: 0.649788 AN: 0.649788

Gnomad4 AMR AF: 0.942 AC: 0.942114 AN: 0.942114

Gnomad4 ASJ AF: 0.966 AC: 0.965726 AN: 0.965726

Gnomad4 EAS AF: 1.00 AC: 0.999613 AN: 0.999613

Gnomad4 SAS AF: 0.981 AC: 0.981366 AN: 0.981366

Gnomad4 FIN AF: 0.996 AC: 0.995578 AN: 0.995578

Gnomad4 NFE AF: 0.986 AC: 0.985978 AN: 0.985978

Gnomad4 OTH AF: 0.919 AC: 0.918638 AN: 0.918638

Alfa AF: 0.939 Hom.: 12602

Bravo AF: 0.873

Asia WGS AF: 0.969 AC: 3370 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

-

Breakthrough Genomics, Breakthrough Genomics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Nov 12, 2018

GeneDx

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified Benign:1

-

PreventionGenetics, part of Exact Sciences

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.94
CADD	Benign	1.2
DANN	Benign	0.62
Mutation Taster		=100/0	polymorphism (auto)

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: rs2592590; hg19: chr2-121729686;