Menu
GeneBe

rs7563724

chr2-232847517-A-G

Variant summary

Our verdict is Benign. Variant got -11 ACMG points: 0P and 11B. BP4_StrongBP6_ModerateBP7BS2

The NM_001103146.3(GIGYF2):c.3630A>G(p.Pro1210=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. PQ1210P?) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.00059 ( 0 hom., cov: 0)
Exomes 𝑓: 0.0012 ( 83 hom. )
Failed GnomAD Quality Control

Consequence

GIGYF2
NM_001103146.3 synonymous

Scores

2

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: -0.0630
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -11 ACMG points.

BP4
?
    BP4 - Multiple lines of computational evidence suggest no impact on gene or gene product (conservation, evolutionary, splicing impact, etc.)
Computational evidence support a benign effect (BayesDel_noAF=-0.85).
BP6
?
    BP6 - Reputable source recently reports variant as benign, but the evidence is not available to the laboratory to perform an independent evaluation
Variant 2-232847517-A-G is Benign according to our data. Variant chr2-232847517-A-G is described in ClinVar as [Benign]. Clinvar id is 3039772.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-232847517-A-G is described in Lovd as [Likely_benign].
BP7
?
    BP7 - A synonymous (silent) variant for which splicing prediction algorithms predict no impact to the splice consensus sequence nor the creation of a new splice site AND the nucleotide is not highly conserved
Synonymous conserved (PhyloP=-0.063 with no splicing effect.
BS2
?
    BS2 - Observed in a healthy adult individual for a recessive (homozygous), dominant (heterozygous), or X-linked (hemizygous) disorder, with full penetrance expected at an early age
High AC in GnomAd at 17 AD gene.

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
GIGYF2NM_001103146.3 linkuse as main transcriptc.3630A>G p.Pro1210= synonymous_variant 27/29 ENST00000373563.9

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
GIGYF2ENST00000373563.9 linkuse as main transcriptc.3630A>G p.Pro1210= synonymous_variant 27/291 NM_001103146.3 P4Q6Y7W6-1

Frequencies

GnomAD3 genomes
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000587
AC:
17
AN:
28976
Hom.:
0
Cov.:
0
show subpopulations
Gnomad AFR
AF:
0.00108
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00139
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000369
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000460
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.00735
AC:
1696
AN:
230696
Hom.:
202
AF XY:
0.00605
AC XY:
762
AN XY:
125968
show subpopulations
Gnomad AFR exome
AF:
0.00825
Gnomad AMR exome
AF:
0.00423
Gnomad ASJ exome
AF:
0.00114
Gnomad EAS exome
AF:
0.0287
Gnomad SAS exome
AF:
0.00514
Gnomad FIN exome
AF:
0.00880
Gnomad NFE exome
AF:
0.00617
Gnomad OTH exome
AF:
0.00519
GnomAD4 exome
Data not reliable, filtered out with message: AS_VQSR
AF:
0.00119
AC:
458
AN:
386294
Hom.:
83
Cov.:
0
AF XY:
0.00126
AC XY:
248
AN XY:
196418
show subpopulations
Gnomad4 AFR exome
AF:
0.000276
Gnomad4 AMR exome
AF:
0.000865
Gnomad4 ASJ exome
AF:
0.000225
Gnomad4 EAS exome
AF:
0.000195
Gnomad4 SAS exome
AF:
0.000369
Gnomad4 FIN exome
AF:
0.0250
Gnomad4 NFE exome
AF:
0.000510
Gnomad4 OTH exome
AF:
0.00159
GnomAD4 genome
?
    Genome Aggregation Database, over 76,156 genomes
AF:
0.000586
AC:
17
AN:
28988
Hom.:
0
Cov.:
0
AF XY:
0.000741
AC XY:
11
AN XY:
14842
show subpopulations
Gnomad4 AFR
AF:
0.00108
Gnomad4 AMR
AF:
0.00138
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000371
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000460
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.0411
Hom.:
3

ClinVar

Significance: Benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

GIGYF2-related disorder Benign:1
Benign, criteria provided, single submitterclinical testingPreventionGenetics, part of Exact SciencesJul 17, 2019This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
Cadd
Benign
1.9
Dann
Benign
0.26
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

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.

Other links and lift over

dbSNP: rs7563724; hg19: chr2-233712227; COSMIC: COSV65247736; COSMIC: COSV65247736; API