Variant 2-232747643-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The ENST00000373563.9(GIGYF2):c.70A>G(p.Ile24Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000062 in 1,613,576 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000033 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000034 ( 0 hom. )

Consequence

GIGYF2
ENST00000373563.9 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 2.77

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.043186486).

BS2

High AC in GnomAd4 at 5 AD gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 linkuse as main transcript	c.70A>G	p.Ile24Val	missense_variant	4/29	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.70A>G	p.Ile24Val	missense_variant	4/29	1	NM_001103146.3	ENSP00000362664	P4	Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.0000329

AC:

AN:

152162

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000121

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000119

AC:

AN:

251318

Hom.:

AF XY:

0.00000736

AC XY:

AN XY:

135822

show subpopulations

Gnomad AFR exome

AF:

0.000185

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000342

AC:

AN:

1461414

Hom.:

Cov.:

AF XY:

0.00000413

AC XY:

AN XY:

727072

show subpopulations

Gnomad4 AFR exome

AF:

0.0000896

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

9.00e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000329

AC:

AN:

152162

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74348

show subpopulations

Gnomad4 AFR

AF:

0.000121

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000329

Hom.:

Bravo

AF:

0.0000340

ExAC

AF:

0.0000165

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

May 27, 2022

The c.70A>G (p.I24V) alteration is located in exon 4 (coding exon 2) of the GIGYF2 gene. This alteration results from a A to G substitution at nucleotide position 70, causing the isoleucine (I) at amino acid position 24 to be replaced by a valine (V). 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

Benign

0.047

BayesDel_addAF

Benign

-0.29

BayesDel_noAF

Benign

-0.41

CADD

Benign

DANN

Benign

0.66

DEOGEN2

Benign

0.045

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

Eigen

Benign

-0.65

Eigen_PC

Benign

-0.32

FATHMM_MKL

Uncertain

0.80

LIST_S2

Benign

0.76

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

M_CAP

Benign

0.0045

MetaRNN

Benign

0.043

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

MetaSVM

Benign

-0.88

MutationTaster

Benign

0.90

D;D;D;D;D;D

PrimateAI

Benign

0.45

PROVEAN

Benign

0.48

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

REVEL

Benign

0.17

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;T

Polyphen

0.0

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

Vest4

0.14

MutPred

0.091

Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);Gain of glycosylation at S26 (P = 0.1174);

MVP

0.15

MPC

0.28

ClinPred

0.077

GERP RS

4.4

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.7

Varity_R

0.036

gMVP

0.58

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