Genetic Variant GIGYF2:p.Gly115Gly (chr2-232756300-G-A) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_ModerateBP6_ModerateBS2

The NM_001103146.3(GIGYF2):c.345G>A(p.Gly115Gly) variant causes a synonymous change. The variant allele was found at a frequency of 0.0000524 in 1,583,560 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.00029 ( 0 hom., cov: 30)

Exomes 𝑓: 0.000027 ( 0 hom. )

Consequence

GIGYF2
NM_001103146.3 synonymous

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 3.96

Publications

1 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 -8 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.37).

BP6

Variant 2-232756300-G-A is Benign according to our data. Variant chr2-232756300-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 3898387.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High AC in GnomAd4 at 44 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.345G>A	p.Gly115Gly	synonymous_variant	Exon 6 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.345G>A	p.Gly115Gly	synonymous_variant	Exon 6 of 29	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.000293

AC:

AN:

150368

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00103

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000132

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000650

AC:

AN:

230638

AF XY:

0.0000240

show subpopulations

Gnomad AFR exome

AF:

0.000835

Gnomad AMR exome

AF:

0.0000677

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000272

AC:

AN:

1433078

Hom.:

Cov.:

AF XY:

0.0000168

AC XY:

AN XY:

712740

show subpopulations

African (AFR)

AF:

0.000980

AC:

AN:

31642

American (AMR)

AF:

0.000102

AC:

AN:

39214

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25122

East Asian (EAS)

AF:

0.00

AC:

AN:

39358

South Asian (SAS)

AF:

0.00

AC:

AN:

80372

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52646

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5310

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1100354

Other (OTH)

AF:

0.0000677

AC:

AN:

59060

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.449

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.000292

AC:

AN:

150482

Hom.:

Cov.:

AF XY:

0.000177

AC XY:

AN XY:

73428

show subpopulations

African (AFR)

AF:

0.00102

AC:

AN:

40990

American (AMR)

AF:

0.000132

AC:

AN:

15124

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3456

East Asian (EAS)

AF:

0.00

AC:

AN:

5134

South Asian (SAS)

AF:

0.00

AC:

AN:

4762

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10134

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

67606

Other (OTH)

AF:

0.00

AC:

AN:

2080

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.000203

Hom.:

Bravo

AF:

0.000355

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Apr 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

GIGYF2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.86

PhyloP100

4.0

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=83/17

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.060

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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2-232756300-G-A

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