Variant rs12328151 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001103146.3(GIGYF2):c.3651G>A(p.Pro1217=) 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:4

Conservation

PhyloP100: -0.437

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -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 id is 518339.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232847538-G-A is described in Lovd as [Benign].

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/exons	MANE	UniProt
GIGYF2	NM_001103146.3 linkuse as main transcript	c.3651G>A	p.Pro1217=	synonymous_variant	27/29	ENST00000373563.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIGYF2	ENST00000373563.9 linkuse as main transcript	c.3651G>A	p.Pro1217=	synonymous_variant	27/29	1	NM_001103146.3	P4	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

GnomAD3 exomes

AF:

0.187

AC:

44473

AN:

237454

Hom.:

4657

AF XY:

0.186

AC XY:

24276

AN XY:

130298

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 SAS exome

AF:

0.0897

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

Gnomad4 AFR exome

AF:

0.0527

Gnomad4 AMR exome

AF:

0.157

Gnomad4 ASJ exome

AF:

0.292

Gnomad4 EAS exome

AF:

0.0975

Gnomad4 SAS exome

AF:

0.0930

Gnomad4 FIN exome

AF:

0.279

Gnomad4 NFE exome

AF:

0.209

Gnomad4 OTH exome

AF:

0.195

GnomAD4 genome

AF:

0.166

AC:

25150

AN:

151192

Hom.:

2607

Cov.:

AF XY:

0.167

AC XY:

12377

AN XY:

73894

show subpopulations

Gnomad4 AFR

AF:

0.0548

Gnomad4 AMR

AF:

0.167

Gnomad4 ASJ

AF:

0.288

Gnomad4 EAS

AF:

0.111

Gnomad4 SAS

AF:

0.0944

Gnomad4 FIN

AF:

0.281

Gnomad4 NFE

AF:

0.219

Gnomad4 OTH

AF:

0.196

Alfa

AF:

0.197

Hom.:

421

Bravo

AF:

0.155

ClinVar

Significance: Benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Parkinson disease 11, autosomal dominant, susceptibility to

Benign:3

Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -
Benign, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
Benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	May 10, 2016	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Jun 09, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.1

DANN

Benign

0.45

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over