rs12328151

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001103146.3(GIGYF2):c.3651G>A(p.Pro1217Pro) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.195 in 1,599,718 control chromosomes in the GnomAD database, including 32,803 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.17 ( 2607 hom., cov: 32)

Exomes 𝑓: 0.20 ( 30196 hom. )

Consequence

GIGYF2
NM_001103146.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: -0.437

Publications

11 publications found

Variant links:

Genes affected

GIGYF2 (HGNC:11960): (GRB10 interacting GYF protein 2) This gene contains CAG trinucleotide repeats and encodes a protein containing several stretches of polyglutamine residues. The encoded protein may be involved in the regulation of tyrosine kinase receptor signaling. This gene is located in a chromosomal region that was genetically linked to Parkinson disease type 11, and mutations in this gene were thought to be causative for this disease. However, more recent studies in different populations have been unable to replicate this association. Alternative splicing results in multiple transcript variants. [provided by RefSeq, May 2013]

GIGYF2 Gene-Disease associations (from GenCC):

Parkinson disease 11, autosomal dominant, susceptibility to
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

GIGYF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.79).

BP6

Variant 2-232847538-G-A is Benign according to our data. Variant chr2-232847538-G-A is described in ClinVar as Benign. ClinVar VariationId is 518339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.437 with no splicing effect.

BA1

GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.216 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.3651G>A	p.Pro1217Pro	synonymous_variant	Exon 27 of 29	ENST00000373563.9	NP_001096616.1	Q6Y7W6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9 link	c.3651G>A	p.Pro1217Pro	synonymous_variant	Exon 27 of 29	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.167

AC:

25157

AN:

151076

Hom.:

2610

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0547

Gnomad AMI

AF:

0.149

Gnomad AMR

AF:

0.167

Gnomad ASJ

AF:

0.288

Gnomad EAS

AF:

0.111

Gnomad SAS

AF:

0.0954

Gnomad FIN

AF:

0.281

Gnomad MID

AF:

0.203

Gnomad NFE

AF:

0.219

Gnomad OTH

AF:

0.198

GnomAD2 exomes

AF:

0.187

AC:

44473

AN:

237454

AF XY:

0.186

show subpopulations

Gnomad AFR exome

AF:

0.0496

Gnomad AMR exome

AF:

0.155

Gnomad ASJ exome

AF:

0.292

Gnomad EAS exome

AF:

0.109

Gnomad FIN exome

AF:

0.293

Gnomad NFE exome

AF:

0.225

Gnomad OTH exome

AF:

0.210

GnomAD4 exome

AF:

0.198

AC:

286085

AN:

1448526

Hom.:

30196

Cov.:

AF XY:

0.196

AC XY:

141278

AN XY:

720744

show subpopulations

African (AFR)

AF:

0.0527

AC:

1750

AN:

33196

American (AMR)

AF:

0.157

AC:

6985

AN:

44388

Ashkenazi Jewish (ASJ)

AF:

0.292

AC:

7443

AN:

25532

East Asian (EAS)

AF:

0.0975

AC:

3848

AN:

39474

South Asian (SAS)

AF:

0.0930

AC:

7967

AN:

85670

European-Finnish (FIN)

AF:

0.279

AC:

14553

AN:

52242

Middle Eastern (MID)

AF:

0.218

AC:

953

AN:

4370

European-Non Finnish (NFE)

AF:

0.209

AC:

230944

AN:

1104042

Other (OTH)

AF:

0.195

AC:

11642

AN:

59612

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.447

Heterozygous variant carriers

11943

23885

35828

47770

59713

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

7650

15300

22950

30600

38250

<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:

0.166

AC:

25150

AN:

151192

Hom.:

2607

Cov.:

AF XY:

0.167

AC XY:

12377

AN XY:

73894

show subpopulations

African (AFR)

AF:

0.0548

AC:

2256

AN:

41200

American (AMR)

AF:

0.167

AC:

2534

AN:

15164

Ashkenazi Jewish (ASJ)

AF:

0.288

AC:

977

AN:

3392

East Asian (EAS)

AF:

0.111

AC:

571

AN:

5142

South Asian (SAS)

AF:

0.0944

AC:

452

AN:

4788

European-Finnish (FIN)

AF:

0.281

AC:

2959

AN:

10530

Middle Eastern (MID)

AF:

0.194

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.219

AC:

14797

AN:

67678

Other (OTH)

AF:

0.196

AC:

411

AN:

2092

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

1031

2061

3092

4122

5153

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

274

548

822

1096

1370

<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:

0.197

Hom.:

421

Bravo

AF:

0.155

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Parkinson disease 11, autosomal dominant, susceptibility to

Benign:3

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 10, 2016

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

not provided

Benign:2

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2021

GeneDx

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

-0.79

CADD

Benign

2.1

(source)

DANN

Benign

0.45

PhyloP100

-0.44

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over