Variant rs775324034 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 8P and 10B. PVS1BP6_ModerateBA1

The ENST00000373563.9(GIGYF2):c.3630_3631insG(p.Gln1211AlafsTer46) variant causes a frameshift change. Variant has been reported in ClinVar as Likely benign (★). Synonymous variant affecting the same amino acid position (i.e. P1210P) has been classified as Benign. Variant results in nonsense mediated mRNA decay.

Frequency

Genomes: 𝑓 0.17 ( 237 hom., cov: 0)

Exomes 𝑓: 0.12 ( 1775 hom. )

Consequence

GIGYF2
ENST00000373563.9 frameshift

Scores

Not classified

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 4.44

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 Likely_benign. Variant got -2 ACMG points.

PVS1

Loss of function variant, product undergoes nonsense mediated mRNA decay. LoF is a known mechanism of disease.

BP6

Variant 2-232847517-A-AG is Benign according to our data. Variant chr2-232847517-A-AG is described in ClinVar as [Likely_benign]. Clinvar id is 402900.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.418 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.3630_3631insG	p.Gln1211AlafsTer46	frameshift_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.3630_3631insG	p.Gln1211AlafsTer46	frameshift_variant	27/29	1	NM_001103146.3	ENSP00000362664	P4	Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.173

AC:

5019

AN:

28964

Hom.:

237

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0445

Gnomad AMI

AF:

0.236

Gnomad AMR

AF:

0.258

Gnomad ASJ

AF:

0.114

Gnomad EAS

AF:

0.439

Gnomad SAS

AF:

0.154

Gnomad FIN

AF:

0.367

Gnomad MID

AF:

0.185

Gnomad NFE

AF:

0.127

Gnomad OTH

AF:

0.185

GnomAD3 exomes

AF:

0.0339

AC:

7827

AN:

230696

Hom.:

334

AF XY:

0.0342

AC XY:

4313

AN XY:

125968

show subpopulations

Gnomad AFR exome

AF:

0.00395

Gnomad AMR exome

AF:

0.0487

Gnomad ASJ exome

AF:

0.0136

Gnomad EAS exome

AF:

0.129

Gnomad SAS exome

AF:

0.0578

Gnomad FIN exome

AF:

0.0452

Gnomad NFE exome

AF:

0.0137

Gnomad OTH exome

AF:

0.0250

GnomAD4 exome

AF:

0.120

AC:

46437

AN:

386888

Hom.:

1775

Cov.:

AF XY:

0.122

AC XY:

23962

AN XY:

196702

show subpopulations

Gnomad4 AFR exome

AF:

0.0313

Gnomad4 AMR exome

AF:

0.333

Gnomad4 ASJ exome

AF:

0.105

Gnomad4 EAS exome

AF:

0.458

Gnomad4 SAS exome

AF:

0.137

Gnomad4 FIN exome

AF:

0.352

Gnomad4 NFE exome

AF:

0.0763

Gnomad4 OTH exome

AF:

0.131

GnomAD4 genome

AF:

0.173

AC:

5019

AN:

28976

Hom.:

237

Cov.:

AF XY:

0.188

AC XY:

2792

AN XY:

14836

show subpopulations

Gnomad4 AFR

AF:

0.0448

Gnomad4 AMR

AF:

0.259

Gnomad4 ASJ

AF:

0.114

Gnomad4 EAS

AF:

0.439

Gnomad4 SAS

AF:

0.154

Gnomad4 FIN

AF:

0.367

Gnomad4 NFE

AF:

0.127

Gnomad4 OTH

AF:

0.170

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Laboratory for Molecular Medicine, Mass General Brigham Personalized Medicine

Mar 28, 2016

Variant identified in a genome or exome case(s) and assessed due to predicted null impact of the variant or pathogenic assertions in the literature or databases. Disclaimer: This variant has not undergone full assessment. The following are preliminary notes: 39.59% east asian with 179 homozygotes in ExAC (VQSRTrancheINDEL96.00to97.00) -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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