dbSNP rs116074753: GIGYF2:p.Asn457Thr (chr2-232794835-A-C) – ACMG Classification: Benign (-8 pts)

Variant summary

Our verdict is Benign. The variant received -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_001103146.3(GIGYF2):c.1370A>C(p.Asn457Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000465 in 1,613,646 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as risk factor (no stars).

Frequency

Genomes: 𝑓 0.00035 ( 0 hom., cov: 32)

Exomes 𝑓: 0.00048 ( 1 hom. )

Consequence

GIGYF2
NM_001103146.3 missense

Scores

Clinical Significance

risk factor no assertion criteria provided O:1

Conservation

PhyloP100: -0.758

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 -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.06393552).

BS2

High AC in GnomAd4 at 53 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.1370A>C	p.Asn457Thr	missense_variant	Exon 13 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.1370A>C	p.Asn457Thr	missense_variant	Exon 13 of 29	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.000349

AC:

AN:

151920

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000262

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000618

Gnomad OTH

AF:

0.000479

GnomAD2 exomes

AF:

0.000394

AC:

AN:

251254

AF XY:

0.000390

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.000202

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0000924

Gnomad NFE exome

AF:

0.000757

Gnomad OTH exome

AF:

0.000489

GnomAD4 exome

AF:

0.000478

AC:

698

AN:

1461608

Hom.:

Cov.:

AF XY:

0.000458

AC XY:

333

AN XY:

727150

show subpopulations

African (AFR)

AF:

0.0000896

AC:

AN:

33470

American (AMR)

AF:

0.000246

AC:

AN:

44720

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

26132

East Asian (EAS)

AF:

0.00

AC:

AN:

39692

South Asian (SAS)

AF:

0.0000232

AC:

AN:

86250

European-Finnish (FIN)

AF:

0.0000749

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00104

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.000584

AC:

649

AN:

1111768

Other (OTH)

AF:

0.000381

AC:

AN:

60388

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.474

Heterozygous variant carriers

113

150

188

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

120

<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:

0.000349

AC:

AN:

152038

Hom.:

Cov.:

AF XY:

0.000336

AC XY:

AN XY:

74320

show subpopulations

African (AFR)

AF:

0.000121

AC:

AN:

41476

American (AMR)

AF:

0.000262

AC:

AN:

15262

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5170

South Asian (SAS)

AF:

0.00

AC:

AN:

4808

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10566

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000618

AC:

AN:

67978

Other (OTH)

AF:

0.000474

AC:

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.511

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Variant carriers

<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:

0.000598

Hom.:

Bravo

AF:

0.000344

TwinsUK

AF:

0.000270

AC:

ALSPAC

AF:

0.000259

AC:

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.00140

AC:

ExAC

AF:

0.000387

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.000872

EpiControl

AF:

0.00101

ClinVar

Significance: risk factor

Submissions summary: Other:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

Parkinson disease 11, autosomal dominant, susceptibility to

Other:1

Aug 01, 2009

OMIM

Significance:risk factor

Review Status:no assertion criteria provided

Collection Method:literature only

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.063

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.56

CADD

Benign

4.7

(source)

DANN

Benign

0.87

DEOGEN2

Benign

0.10

.;T;.;T;T;.;.;T

Eigen

Benign

-1.1

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.060

LIST_S2

Benign

0.72

T;.;.;T;T;T;T;T

M_CAP

Benign

0.018

MetaRNN

Benign

0.064

T;T;T;T;T;T;T;T

MetaSVM

Benign

-0.95

PhyloP100

-0.76

PrimateAI

Benign

0.25

PROVEAN

Benign

-0.41

.;N;N;N;N;N;N;N

REVEL

Benign

0.026

Sift

Benign

0.32

.;T;T;T;T;T;T;T

Sift4G

Benign

0.41

T;T;T;T;T;T;T;T

Polyphen

0.0

.;B;.;B;.;.;.;.

Vest4

0.13

MVP

0.26

MPC

0.33

ClinPred

0.012

GERP RS

-3.7

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.022

gMVP

0.11

Mutation Taster

=100/0

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.070

Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

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