2-232749065-T-C

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -6 ACMG points: 0P and 6B. BP4_ModerateBS2

The NM_001103146.3(GIGYF2):c.250T>C(p.Phe84Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000261 in 1,570,738 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000026 ( 0 hom. )

Consequence

GIGYF2
NM_001103146.3 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.24

Publications

2 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: Likely_benign. The variant received -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.11722872).

BS2

High AC in GnomAdExome4 at 37 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.250T>C	p.Phe84Leu	missense_variant	Exon 5 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.250T>C	p.Phe84Leu	missense_variant	Exon 5 of 29	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.00000796

AC:

AN:

251390

AF XY:

0.00000736

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000261

AC:

AN:

1418556

Hom.:

Cov.:

AF XY:

0.0000325

AC XY:

AN XY:

708456

show subpopulations

African (AFR)

AF:

0.0000307

AC:

AN:

32586

American (AMR)

AF:

0.00

AC:

AN:

44680

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25866

East Asian (EAS)

AF:

0.00

AC:

AN:

39456

South Asian (SAS)

AF:

0.00

AC:

AN:

85428

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53396

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5674

European-Non Finnish (NFE)

AF:

0.0000336

AC:

AN:

1072530

Other (OTH)

AF:

0.00

AC:

AN:

58940

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.471

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.0000263

AC:

AN:

152182

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74354

show subpopulations

African (AFR)

AF:

0.0000241

AC:

AN:

41450

American (AMR)

AF:

0.00

AC:

AN:

15280

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3466

East Asian (EAS)

AF:

0.00

AC:

AN:

5200

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10614

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.0000441

AC:

AN:

68032

Other (OTH)

AF:

0.00

AC:

AN:

2086

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.0000580

Hom.:

Bravo

AF:

0.0000227

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Dec 19, 2023

Ambry Genetics

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

The c.250T>C (p.F84L) alteration is located in exon 5 (coding exon 3) of the GIGYF2 gene. This alteration results from a T to C substitution at nucleotide position 250, causing the phenylalanine (F) at amino acid position 84 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.88

BayesDel_addAF

Uncertain

0.056

BayesDel_noAF

Benign

-0.14

CADD

Uncertain

(source)

DANN

Benign

0.72

DEOGEN2

Benign

0.057

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

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.016

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Benign

0.83

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

M_CAP

Benign

0.019

MetaRNN

Benign

0.12

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

MetaSVM

Benign

-0.71

PhyloP100

6.2

PrimateAI

Pathogenic

0.87

PROVEAN

Benign

0.45

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

REVEL

Benign

0.28

Sift

Benign

1.0

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

Sift4G

Benign

1.0

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

Polyphen

0.95

.;P;.;.;.;.;.;P;.;.;.;.;.

Vest4

0.45

MutPred

0.21

Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);Gain of disorder (P = 0.0913);

MVP

0.21

MPC

0.38

ClinPred

0.20

GERP RS

5.8

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.49

gMVP

0.56

Mutation Taster

=50/50

(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

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

2-232749065-T-C

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