rs2305137
Positions:
Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_001103146.3(GIGYF2):c.3461-9G>A variant causes a splice polypyrimidine tract, intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.637 in 1,606,238 control chromosomes in the GnomAD database, including 330,907 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.65 ( 32610 hom., cov: 32)
Exomes 𝑓: 0.64 ( 298297 hom. )
Consequence
GIGYF2
NM_001103146.3 splice_polypyrimidine_tract, intron
NM_001103146.3 splice_polypyrimidine_tract, intron
Scores
2
Splicing: ADA: 0.0003926
2
Clinical Significance
Conservation
PhyloP100: -0.901
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 -20 ACMG points.
BP4
?
Computational evidence support a benign effect (BayesDel_noAF=-0.87).
BP6
?
Variant 2-232847339-G-A is Benign according to our data. Variant chr2-232847339-G-A is described in ClinVar as [Benign]. Clinvar id is 518337.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr2-232847339-G-A is described in Lovd as [Benign].
BA1
?
GnomAd4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.685 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GIGYF2 | NM_001103146.3 | c.3461-9G>A | splice_polypyrimidine_tract_variant, intron_variant | ENST00000373563.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GIGYF2 | ENST00000373563.9 | c.3461-9G>A | splice_polypyrimidine_tract_variant, intron_variant | 1 | NM_001103146.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.652 AC: 99004AN: 151850Hom.: 32585 Cov.: 32
GnomAD3 genomes
?
AF:
AC:
99004
AN:
151850
Hom.:
Cov.:
32
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.642 AC: 161496AN: 251378Hom.: 53636 AF XY: 0.626 AC XY: 85067AN XY: 135868
GnomAD3 exomes
AF:
AC:
161496
AN:
251378
Hom.:
AF XY:
AC XY:
85067
AN XY:
135868
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.635 AC: 923521AN: 1454270Hom.: 298297 Cov.: 34 AF XY: 0.627 AC XY: 454117AN XY: 723992
GnomAD4 exome
AF:
AC:
923521
AN:
1454270
Hom.:
Cov.:
34
AF XY:
AC XY:
454117
AN XY:
723992
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome ? AF: 0.652 AC: 99082AN: 151968Hom.: 32610 Cov.: 32 AF XY: 0.654 AC XY: 48558AN XY: 74272
GnomAD4 genome
?
AF:
AC:
99082
AN:
151968
Hom.:
Cov.:
32
AF XY:
AC XY:
48558
AN XY:
74272
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Alfa
AF:
Hom.:
Bravo
AF:
Asia WGS
AF:
AC:
1733
AN:
3478
EpiCase
AF:
EpiControl
AF:
ClinVar
Significance: Benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
Parkinson disease 11, autosomal dominant, susceptibility to Benign:3
Benign, no assertion criteria provided | clinical testing | Diagnostic Laboratory, Department of Genetics, University Medical Center Groningen | - | - - |
Benign, criteria provided, single submitter | clinical testing | Clinical Genetics DNA and cytogenetics Diagnostics Lab, Erasmus MC, Erasmus Medical Center | May 31, 2017 | - - |
Benign, no assertion criteria provided | clinical testing | Genome Diagnostics Laboratory, Amsterdam University Medical Center | Mar 21, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | GeneDx | Jun 09, 2021 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
RBP_binding_hub_radar
RBP_regulation_power_radar
Splicing
Name
Calibrated prediction
Score
Prediction
dbscSNV1_ADA
Benign
dbscSNV1_RF
Benign
SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at