chr2-232819834-C-T

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 1P and 4B. PP5BS2

The NM_001103146.3(GIGYF2):c.2378C>T(p.Ala793Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000594 in 1,262,988 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Conflicting classifications of pathogenicity (no stars).

Frequency

Genomes: 𝑓 0.000060 ( 0 hom., cov: 26)

Exomes 𝑓: 0.000059 ( 1 hom. )

Consequence

GIGYF2
NM_001103146.3 missense

Scores

Clinical Significance

Conflicting classifications of pathogenicity criteria provided, conflicting classifications P:1U:3

Conservation

PhyloP100: 5.06

Publications

7 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 -3 ACMG points.

PP5

Variant 2-232819834-C-T is Pathogenic according to our data. Variant chr2-232819834-C-T is described in ClinVar as Conflicting_classifications_of_pathogenicity. ClinVar VariationId is 216934.

BS2

High AC in GnomAd4 at 7 AD,Unknown gene.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GIGYF2	NM_001103146.3 link	c.2378C>T	p.Ala793Val	missense_variant	Exon 21 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.2378C>T	p.Ala793Val	missense_variant	Exon 21 of 29	1	NM_001103146.3	ENSP00000362664.5		Q6Y7W6-1

Frequencies

GnomAD3 genomes

AF:

0.0000682

AC:

AN:

117378

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000119

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000306

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00806

Gnomad NFE

AF:

0.0000808

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000534

AC:

AN:

243350

AF XY:

0.0000683

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.0000613

Gnomad ASJ exome

AF:

0.000100

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000721

Gnomad OTH exome

AF:

0.000170

GnomAD4 exome

AF:

0.0000594

AC:

AN:

1145554

Hom.:

Cov.:

AF XY:

0.0000579

AC XY:

AN XY:

570390

show subpopulations

African (AFR)

AF:

0.0000805

AC:

AN:

24834

American (AMR)

AF:

0.000108

AC:

AN:

37060

Ashkenazi Jewish (ASJ)

AF:

0.0000580

AC:

AN:

17230

East Asian (EAS)

AF:

0.00

AC:

AN:

18624

South Asian (SAS)

AF:

0.0000247

AC:

AN:

81000

European-Finnish (FIN)

AF:

0.00

AC:

AN:

35086

Middle Eastern (MID)

AF:

0.00589

AC:

AN:

4074

European-Non Finnish (NFE)

AF:

0.0000339

AC:

AN:

885214

Other (OTH)

AF:

0.000118

AC:

AN:

42432

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

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

GnomAD4 genome

AF:

0.0000596

AC:

AN:

117434

Hom.:

Cov.:

AF XY:

0.0000928

AC XY:

AN XY:

53904

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

30054

American (AMR)

AF:

0.000119

AC:

AN:

8390

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3262

East Asian (EAS)

AF:

0.00

AC:

AN:

3394

South Asian (SAS)

AF:

0.000306

AC:

AN:

3270

European-Finnish (FIN)

AF:

0.00

AC:

AN:

4632

Middle Eastern (MID)

AF:

0.00

AC:

AN:

120

European-Non Finnish (NFE)

AF:

0.0000808

AC:

AN:

61908

Other (OTH)

AF:

0.00

AC:

AN:

1550

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.513

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:

0.0000959

Hom.:

Bravo

AF:

0.0000416

ExAC

AF:

0.0000247

AC:

ClinVar

Significance: Conflicting classifications of pathogenicity

Submissions summary: Pathogenic:1Uncertain:3

Revision: criteria provided, conflicting classifications

LINK: link

Submissions by phenotype

Parkinson disease 11, autosomal dominant, susceptibility to

Pathogenic:1Uncertain:2

Feb 11, 2020

Al Jalila Children’s Genomics Center, Al Jalila Childrens Speciality Hospital

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Apr 16, 2013

UCLA Clinical Genomics Center, UCLA

Significance:Likely pathogenic

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 22, 2024

Genomic Medicine Center of Excellence, King Faisal Specialist Hospital and Research Centre

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

not provided

Uncertain:1

Sep 01, 2023

CeGaT Center for Human Genetics Tuebingen

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.15

BayesDel_addAF

Benign

-0.087

BayesDel_noAF

Benign

-0.18

CADD

Pathogenic

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.12

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

Eigen

Uncertain

0.35

Eigen_PC

Uncertain

0.41

FATHMM_MKL

Pathogenic

0.99

LIST_S2

Uncertain

0.95

D;.;.;D;D;D;D

M_CAP

Uncertain

0.094

MetaRNN

Benign

0.32

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

MetaSVM

Uncertain

-0.21

PhyloP100

5.1

PrimateAI

Uncertain

0.78

PROVEAN

Benign

-0.92

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

REVEL

Uncertain

0.36

Sift

Benign

0.043

.;D;D;D;D;D;D

Sift4G

Benign

0.25

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

Polyphen

0.89

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

Vest4

0.51

MVP

0.29

MPC

0.30

ClinPred

0.34

GERP RS

5.0

Varity_R

0.31

gMVP

0.16

Mutation Taster

=0/100

disease causing (ClinVar)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.21

Details are displayed if max score is > 0.2

DS_AG_spliceai

0.21

Position offset: -3

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