Variant 2-232847517-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6BP7BS2

The ENST00000373563.9(GIGYF2):c.3630A>G(p.Pro1210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars). Synonymous variant affecting the same amino acid position (i.e. PQ1210P?) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0012 ( 83 hom. )

Failed GnomAD Quality Control

Consequence

GIGYF2
ENST00000373563.9 synonymous

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.0630

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 -10 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.85).

BP6

Variant 2-232847517-A-G is Benign according to our data. Variant chr2-232847517-A-G is described in ClinVar as [Benign]. Clinvar id is 3039772.Status of the report is no_assertion_criteria_provided, 0 stars. Variant chr2-232847517-A-G is described in Lovd as [Likely_benign].

BP7

Synonymous conserved (PhyloP=-0.063 with no splicing effect.

BS2

High AC in GnomAd4 at 17 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 linkuse as main transcript	c.3630A>G	p.Pro1210=	synonymous_variant	27/29	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.3630A>G	p.Pro1210=	synonymous_variant	27/29	1	NM_001103146.3	ENSP00000362664	P4	Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.000587

AC:

AN:

28976

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00108

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00139

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000369

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000460

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00735

AC:

1696

AN:

230696

Hom.:

202

AF XY:

0.00605

AC XY:

762

AN XY:

125968

show subpopulations

Gnomad AFR exome

AF:

0.00825

Gnomad AMR exome

AF:

0.00423

Gnomad ASJ exome

AF:

0.00114

Gnomad EAS exome

AF:

0.0287

Gnomad SAS exome

AF:

0.00514

Gnomad FIN exome

AF:

0.00880

Gnomad NFE exome

AF:

0.00617

Gnomad OTH exome

AF:

0.00519

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00119

AC:

458

AN:

386294

Hom.:

Cov.:

AF XY:

0.00126

AC XY:

248

AN XY:

196418

show subpopulations

Gnomad4 AFR exome

AF:

0.000276

Gnomad4 AMR exome

AF:

0.000865

Gnomad4 ASJ exome

AF:

0.000225

Gnomad4 EAS exome

AF:

0.000195

Gnomad4 SAS exome

AF:

0.000369

Gnomad4 FIN exome

AF:

0.0250

Gnomad4 NFE exome

AF:

0.000510

Gnomad4 OTH exome

AF:

0.00159

GnomAD4 genome

AF:

0.000586

AC:

AN:

28988

Hom.:

Cov.:

AF XY:

0.000741

AC XY:

AN XY:

14842

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00138

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000371

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000460

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0411

Hom.:

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

GIGYF2-related disorder

Benign:1

Benign, no assertion criteria provided

clinical testing

PreventionGenetics, part of Exact Sciences

Jul 17, 2019

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.85

CADD

Benign

1.9

DANN

Benign

0.26

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

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