chr2-120955454-G-A

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

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

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: 0.372

Publications

8 publications found

Variant links:

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]

GLI2 Gene-Disease associations (from GenCC):

holoprosencephaly 9
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE Submitted by: G2P, Labcorp Genetics (formerly Invitae), Ambry Genetics
postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome
Inheritance: AD Classification: DEFINITIVE, STRONG, MODERATE, SUPPORTIVE, LIMITED Submitted by: Orphanet, Labcorp Genetics (formerly Invitae), Ambry Genetics, Illumina
combined pituitary hormone deficiencies, genetic form
Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
holoprosencephaly
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

GLI2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId 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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001374353.1. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLI2	NM_001374353.1	MANE Select	c.643+24G>A	intron	N/A	NP_001361282.1	A0A7I2PJA1
GLI2	NM_001371271.1		c.643+24G>A	intron	N/A	NP_001358200.1	P10070-5
GLI2	NM_005270.5		c.643+24G>A	intron	N/A	NP_005261.2	P10070-5

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
GLI2	ENST00000361492.9	TSL:1 MANE Select	c.643+24G>A	intron	N/A	ENSP00000354586.5	A0A7I2PJA1
GLI2	ENST00000360874.10	TSL:1	n.231-13260G>A	intron	N/A
GLI2	ENST00000433812.1	TSL:1	n.*342+24G>A	intron	N/A	ENSP00000402383.1	H7C1U2

Frequencies

GnomAD3 genomes

AF:

0.788

AC:

119845

AN:

152094

Hom.:

52059

Cov.:

show subpopulations

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

GnomAD2 exomes

AF:

0.916

AC:

166619

AN:

181970

AF XY:

0.925

show subpopulations

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 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.:

AF XY:

0.935

AC XY:

623114

AN XY:

666244

show subpopulations

African (AFR)

AF:

0.350

AC:

10631

AN:

30380

American (AMR)

AF:

0.930

AC:

33837

AN:

36366

Ashkenazi Jewish (ASJ)

AF:

0.890

AC:

20700

AN:

23266

East Asian (EAS)

AF:

1.00

AC:

37691

AN:

37700

South Asian (SAS)

AF:

0.954

AC:

74580

AN:

78194

European-Finnish (FIN)

AF:

0.974

AC:

48182

AN:

49466

Middle Eastern (MID)

AF:

0.896

AC:

4852

AN:

5418

European-Non Finnish (NFE)

AF:

0.947

AC:

972419

AN:

1026778

Other (OTH)

AF:

0.905

AC:

50440

AN:

55708

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.489

Heterozygous variant carriers

3418

6836

10254

13672

17090

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

19856

39712

59568

79424

99280

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.788

AC:

119872

AN:

152212

Hom.:

52062

Cov.:

AF XY:

0.795

AC XY:

59148

AN XY:

74424

show subpopulations

African (AFR)

AF:

0.380

AC:

15770

AN:

41512

American (AMR)

AF:

0.886

AC:

13557

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.886

AC:

3077

AN:

3472

East Asian (EAS)

AF:

0.999

AC:

5133

AN:

5140

South Asian (SAS)

AF:

0.957

AC:

4622

AN:

4830

European-Finnish (FIN)

AF:

0.979

AC:

10399

AN:

10624

Middle Eastern (MID)

AF:

0.867

AC:

255

AN:

294

European-Non Finnish (NFE)

AF:

0.946

AC:

64375

AN:

68016

Other (OTH)

AF:

0.841

AC:

1777

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.496

Heterozygous variant carriers

806

1612

2419

3225

4031

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

830

1660

2490

3320

4150

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.713

Hom.:

12477

Bravo

AF:

0.762

Asia WGS

AF:

0.933

AC:

3243

AN:

3478

ClinVar

ClinVar submissions

Significance:Benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

Holoprosencephaly 9 (1)

not specified (1)

Postaxial polydactyly-anterior pituitary anomalies-facial dysmorphism syndrome (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.84

CADD

Benign

5.1

(source)

DANN

Benign

0.50

PhyloP100

0.37

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over