rs2305137

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_001103146.3(GIGYF2):c.3461-9G>A variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,606,238 control chromosomes in the GnomAD database, including 330,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.65 ( 32610 hom., cov: 32)

Exomes 𝑓: 0.64 ( 298297 hom. )

Consequence

GIGYF2
NM_001103146.3 intron

Scores

Splicing: ADA: 0.0003926

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.901

Publications

14 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 -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.87).

BP6

Variant 2-232847339-G-A is Benign according to our data. Variant chr2-232847339-G-A is described in ClinVar as [Benign]. Clinvar id is 518337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.3461-9G>A		intron_variant	Intron 26 of 28	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.3461-9G>A		intron_variant	Intron 26 of 28	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.652

AC:

99004

AN:

151850

Hom.:

32585

Cov.:

show subpopulations

Gnomad AFR

AF:

0.626

Gnomad AMI

AF:

0.634

Gnomad AMR

AF:

0.696

Gnomad ASJ

AF:

0.665

Gnomad EAS

AF:

0.668

Gnomad SAS

AF:

0.377

Gnomad FIN

AF:

0.768

Gnomad MID

AF:

0.637

Gnomad NFE

AF:

0.658

Gnomad OTH

AF:

0.667

GnomAD2 exomes

AF:

0.642

AC:

161496

AN:

251378

AF XY:

0.626

show subpopulations

Gnomad AFR exome

AF:

0.624

Gnomad AMR exome

AF:

0.742

Gnomad ASJ exome

AF:

0.664

Gnomad EAS exome

AF:

0.673

Gnomad FIN exome

AF:

0.766

Gnomad NFE exome

AF:

0.660

Gnomad OTH exome

AF:

0.649

GnomAD4 exome

AF:

0.635

AC:

923521

AN:

1454270

Hom.:

298297

Cov.:

AF XY:

0.627

AC XY:

454117

AN XY:

723992

show subpopulations

African (AFR)

AF:

0.622

AC:

20735

AN:

33314

American (AMR)

AF:

0.737

AC:

32966

AN:

44708

Ashkenazi Jewish (ASJ)

AF:

0.669

AC:

17432

AN:

26070

East Asian (EAS)

AF:

0.709

AC:

28120

AN:

39662

South Asian (SAS)

AF:

0.371

AC:

31960

AN:

86100

European-Finnish (FIN)

AF:

0.764

AC:

40827

AN:

53414

Middle Eastern (MID)

AF:

0.568

AC:

2868

AN:

5046

European-Non Finnish (NFE)

AF:

0.643

AC:

710995

AN:

1105898

Other (OTH)

AF:

0.626

AC:

37618

AN:

60058

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.454

Heterozygous variant carriers

15997

31994

47990

63987

79984

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

18564

37128

55692

74256

92820

<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:

0.652

AC:

99082

AN:

151968

Hom.:

32610

Cov.:

AF XY:

0.654

AC XY:

48558

AN XY:

74272

show subpopulations

African (AFR)

AF:

0.626

AC:

25917

AN:

41406

American (AMR)

AF:

0.696

AC:

10627

AN:

15264

Ashkenazi Jewish (ASJ)

AF:

0.665

AC:

2309

AN:

3472

East Asian (EAS)

AF:

0.668

AC:

3455

AN:

5170

South Asian (SAS)

AF:

0.376

AC:

1812

AN:

4814

European-Finnish (FIN)

AF:

0.768

AC:

8109

AN:

10564

Middle Eastern (MID)

AF:

0.640

AC:

187

AN:

292

European-Non Finnish (NFE)

AF:

0.658

AC:

44696

AN:

67962

Other (OTH)

AF:

0.659

AC:

1394

AN:

2116

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1738

3477

5215

6954

8692

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

786

1572

2358

3144

3930

<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:

0.661

Hom.:

19073

Bravo

AF:

0.656

Asia WGS

AF:

0.498

AC:

1733

AN:

3478

EpiCase

AF:

0.651

EpiControl

AF:

0.656

ClinVar

Significance: Benign

Submissions summary: Benign:5

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

Parkinson disease 11, autosomal dominant, susceptibility to

Benign:3

Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

Mar 21, 2016

Genome Diagnostics Laboratory, Amsterdam University Medical Center

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

- -

May 31, 2017

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

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Jun 09, 2021

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.87

CADD

Benign

0.034

(source)

DANN

Benign

0.40

PhyloP100

-0.90

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Benign

0.00039

dbscSNV1_RF

Benign

0.0020

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