Variant rs2305138 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.1554G>A(p.Glu518=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0655 in 1,599,972 control chromosomes in the GnomAD database, including 4,052 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.079 ( 614 hom., cov: 32)

Exomes 𝑓: 0.064 ( 3438 hom. )

Consequence

GIGYF2
NM_001103146.3 synonymous

Scores

Clinical Significance

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

Conservation

PhyloP100: 2.05

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=-0.49).

BP6

Variant 2-232796136-G-A is Benign according to our data. Variant chr2-232796136-G-A is described in ClinVar as [Benign]. Clinvar id is 522283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232796136-G-A is described in Lovd as [Benign]. Variant chr2-232796136-G-A is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=2.05 with no splicing effect.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.163 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 linkuse as main transcript	c.1554G>A	p.Glu518=	synonymous_variant	14/29	ENST00000373563.9	NP_001096616.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9 linkuse as main transcript	c.1554G>A	p.Glu518=	synonymous_variant	14/29	1	NM_001103146.3	ENSP00000362664	P4	Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.0793

AC:

12062

AN:

152078

Hom.:

612

Cov.:

show subpopulations

Gnomad AFR

AF:

0.120

Gnomad AMI

AF:

0.108

Gnomad AMR

AF:

0.0489

Gnomad ASJ

AF:

0.0196

Gnomad EAS

AF:

0.173

Gnomad SAS

AF:

0.0700

Gnomad FIN

AF:

0.0793

Gnomad MID

AF:

0.0285

Gnomad NFE

AF:

0.0581

Gnomad OTH

AF:

0.0684

GnomAD3 exomes

AF:

0.0708

AC:

17778

AN:

251254

Hom.:

868

AF XY:

0.0687

AC XY:

9331

AN XY:

135802

show subpopulations

Gnomad AFR exome

AF:

0.126

Gnomad AMR exome

AF:

0.0478

Gnomad ASJ exome

AF:

0.0237

Gnomad EAS exome

AF:

0.189

Gnomad SAS exome

AF:

0.0576

Gnomad FIN exome

AF:

0.0805

Gnomad NFE exome

AF:

0.0575

Gnomad OTH exome

AF:

0.0545

GnomAD4 exome

AF:

0.0640

AC:

92693

AN:

1447776

Hom.:

3438

Cov.:

AF XY:

0.0636

AC XY:

45874

AN XY:

721214

show subpopulations

Gnomad4 AFR exome

AF:

0.126

Gnomad4 AMR exome

AF:

0.0470

Gnomad4 ASJ exome

AF:

0.0242

Gnomad4 EAS exome

AF:

0.172

Gnomad4 SAS exome

AF:

0.0605

Gnomad4 FIN exome

AF:

0.0787

Gnomad4 NFE exome

AF:

0.0595

Gnomad4 OTH exome

AF:

0.0667

GnomAD4 genome

AF:

0.0794

AC:

12079

AN:

152196

Hom.:

614

Cov.:

AF XY:

0.0807

AC XY:

6003

AN XY:

74402

show subpopulations

Gnomad4 AFR

AF:

0.120

Gnomad4 AMR

AF:

0.0488

Gnomad4 ASJ

AF:

0.0196

Gnomad4 EAS

AF:

0.172

Gnomad4 SAS

AF:

0.0696

Gnomad4 FIN

AF:

0.0793

Gnomad4 NFE

AF:

0.0581

Gnomad4 OTH

AF:

0.0681

Alfa

AF:

0.0609

Hom.:

615

Bravo

AF:

0.0814

Asia WGS

AF:

0.0980

AC:

341

AN:

3478

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:2

Likely benign, no assertion criteria provided	clinical testing	Genome Diagnostics Laboratory, Amsterdam University Medical Center	Apr 21, 2016	- -
Benign, criteria provided, single submitter	clinical testing	Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center	Sep 21, 2015	- -

not provided

Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 09, 2021	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.9

DANN

Benign

0.52

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