rs3816334

Variant summary

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

The NM_001103146.3(GIGYF2):c.2940A>G(p.Gln980=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.64 in 1,601,720 control chromosomes in the GnomAD database, including 332,040 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.68 ( 35868 hom., cov: 32)

Exomes 𝑓: 0.64 ( 296172 hom. )

Consequence

GIGYF2
NM_001103146.3 synonymous

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: 1.01

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:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.64).

BP6

Variant 2-232844096-A-G is Benign according to our data. Variant chr2-232844096-A-G is described in ClinVar as [Benign]. Clinvar id is 518336.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232844096-A-G is described in Lovd as [Benign].

BP7

Synonymous conserved (PhyloP=1.01 with no splicing effect.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.727 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.2940A>G	p.Gln980=	synonymous_variant	24/29	ENST00000373563.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GIGYF2	ENST00000373563.9 linkuse as main transcript	c.2940A>G	p.Gln980=	synonymous_variant	24/29	1	NM_001103146.3	P4	Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.683

AC:

103784

AN:

151868

Hom.:

35824

Cov.:

show subpopulations

Gnomad AFR

AF:

0.734

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.709

Gnomad ASJ

AF:

0.665

Gnomad EAS

AF:

0.667

Gnomad SAS

AF:

0.378

Gnomad FIN

AF:

0.767

Gnomad MID

AF:

0.636

Gnomad NFE

AF:

0.659

Gnomad OTH

AF:

0.689

GnomAD3 exomes

AF:

0.650

AC:

157128

AN:

241644

Hom.:

52536

AF XY:

0.632

AC XY:

82393

AN XY:

130466

show subpopulations

Gnomad AFR exome

AF:

0.736

Gnomad AMR exome

AF:

0.748

Gnomad ASJ exome

AF:

0.664

Gnomad EAS exome

AF:

0.673

Gnomad SAS exome

AF:

0.363

Gnomad FIN exome

AF:

0.765

Gnomad NFE exome

AF:

0.659

Gnomad OTH exome

AF:

0.654

GnomAD4 exome

AF:

0.636

AC:

921477

AN:

1449734

Hom.:

296172

Cov.:

AF XY:

0.628

AC XY:

452438

AN XY:

720936

show subpopulations

Gnomad4 AFR exome

AF:

0.727

Gnomad4 AMR exome

AF:

0.744

Gnomad4 ASJ exome

AF:

0.667

Gnomad4 EAS exome

AF:

0.708

Gnomad4 SAS exome

AF:

0.371

Gnomad4 FIN exome

AF:

0.764

Gnomad4 NFE exome

AF:

0.640

Gnomad4 OTH exome

AF:

0.632

GnomAD4 genome

AF:

0.683

AC:

103878

AN:

151986

Hom.:

35868

Cov.:

AF XY:

0.684

AC XY:

50846

AN XY:

74294

show subpopulations

Gnomad4 AFR

AF:

0.734

Gnomad4 AMR

AF:

0.710

Gnomad4 ASJ

AF:

0.665

Gnomad4 EAS

AF:

0.667

Gnomad4 SAS

AF:

0.377

Gnomad4 FIN

AF:

0.767

Gnomad4 NFE

AF:

0.659

Gnomad4 OTH

AF:

0.681

Alfa

AF:

0.670

Hom.:

43627

Bravo

AF:

0.691

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, no assertion criteria provided	clinical testing	Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen	-	- -
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	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Jun 22, 2017	- -

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Mar 03, 2020

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.64

Cadd

Benign

5.9

Dann

Benign

0.22

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