rs2305138

Variant names:

Variant summary

Our verdict is Benign. The variant received -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BA1

The NM_001103146.3(GIGYF2):c.1554G>A(p.Glu518Glu) 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

Publications

16 publications found

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 Gene-Disease associations (from GenCC):

Parkinson disease 11, autosomal dominant, susceptibility to
Inheritance: AD, Unknown Classification: MODERATE, LIMITED Submitted by: Ambry Genetics, Labcorp Genetics (formerly Invitae), Genomics England PanelApp

GIGYF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -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 VariationId is 522283.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

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 rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.1554G>A	p.Glu518Glu	synonymous_variant	Exon 14 of 29	ENST00000373563.9	NP_001096616.1	Q6Y7W6-1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
GIGYF2	ENST00000373563.9 link	c.1554G>A	p.Glu518Glu	synonymous_variant	Exon 14 of 29	1	NM_001103146.3	ENSP00000362664.5		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

GnomAD2 exomes

AF:

0.0708

AC:

17778

AN:

251254

AF XY:

0.0687

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 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

African (AFR)

AF:

0.126

AC:

4191

AN:

33184

American (AMR)

AF:

0.0470

AC:

2103

AN:

44704

Ashkenazi Jewish (ASJ)

AF:

0.0242

AC:

630

AN:

26072

East Asian (EAS)

AF:

0.172

AC:

6801

AN:

39594

South Asian (SAS)

AF:

0.0605

AC:

5196

AN:

85948

European-Finnish (FIN)

AF:

0.0787

AC:

4203

AN:

53394

Middle Eastern (MID)

AF:

0.0280

AC:

161

AN:

5748

European-Non Finnish (NFE)

AF:

0.0595

AC:

65408

AN:

1099202

Other (OTH)

AF:

0.0667

AC:

4000

AN:

59930

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.483

Heterozygous variant carriers

4215

8429

12644

16858

21073

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

2580

5160

7740

10320

12900

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0794

AC:

12079

AN:

152196

Hom.:

614

Cov.:

AF XY:

0.0807

AC XY:

6003

AN XY:

74402

show subpopulations

African (AFR)

AF:

0.120

AC:

4994

AN:

41508

American (AMR)

AF:

0.0488

AC:

747

AN:

15296

Ashkenazi Jewish (ASJ)

AF:

0.0196

AC:

AN:

3472

East Asian (EAS)

AF:

0.172

AC:

891

AN:

5170

South Asian (SAS)

AF:

0.0696

AC:

336

AN:

4826

European-Finnish (FIN)

AF:

0.0793

AC:

839

AN:

10584

Middle Eastern (MID)

AF:

0.0306

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.0581

AC:

3953

AN:

68022

Other (OTH)

AF:

0.0681

AC:

144

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.499

Heterozygous variant carriers

540

1080

1620

2160

2700

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

142

284

426

568

710

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0648

Hom.:

1515

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

Apr 21, 2016

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Likely benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Sep 21, 2015

Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Benign:2

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.49

CADD

Benign

6.9

(source)

DANN

Benign

0.52

PhyloP100

2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Mutation Taster

=97/3

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over