chr2-232747646-A-G
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2
The NM_001103146.3(GIGYF2):c.73A>G(p.Thr25Ala) variant causes a missense change. The variant allele was found at a frequency of 0.000148 in 1,613,684 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).
Frequency
Genomes: 𝑓 0.00024 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00014 ( 0 hom. )
Consequence
GIGYF2
NM_001103146.3 missense
NM_001103146.3 missense
Scores
2
12
Clinical Significance
Conservation
PhyloP100: 5.10
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]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -10 ACMG points.
BP4
?
Computational evidence support a benign effect (MetaRNN=0.0057192445).
BP6
?
Variant 2-232747646-A-G is Benign according to our data. Variant chr2-232747646-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 3050052.Status of the report is criteria_provided_single_submitter, 1 stars. Variant chr2-232747646-A-G is described in Lovd as [Likely_benign].
BS2
?
High AC in GnomAd at 36 AD gene.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
GIGYF2 | NM_001103146.3 | c.73A>G | p.Thr25Ala | missense_variant | 4/29 | ENST00000373563.9 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
GIGYF2 | ENST00000373563.9 | c.73A>G | p.Thr25Ala | missense_variant | 4/29 | 1 | NM_001103146.3 | P4 |
Frequencies
GnomAD3 genomes ? AF: 0.000237 AC: 36AN: 152202Hom.: 0 Cov.: 32
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GnomAD3 exomes AF: 0.000481 AC: 121AN: 251318Hom.: 1 AF XY: 0.000486 AC XY: 66AN XY: 135826
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GnomAD4 exome AF: 0.000139 AC: 203AN: 1461364Hom.: 0 Cov.: 31 AF XY: 0.000144 AC XY: 105AN XY: 727030
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GnomAD4 genome ? AF: 0.000236 AC: 36AN: 152320Hom.: 0 Cov.: 32 AF XY: 0.000242 AC XY: 18AN XY: 74498
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ClinVar
Significance: Likely benign
Submissions summary: Benign:1
Revision: criteria provided, single submitter
LINK: link
Submissions by phenotype
GIGYF2-related disorder Benign:1
Likely benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jul 10, 2019 | This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
BayesDel_addAF
Benign
T
BayesDel_noAF
Benign
Cadd
Benign
Dann
Uncertain
Eigen
Benign
Eigen_PC
Benign
FATHMM_MKL
Benign
D
LIST_S2
Benign
T;.;T;T;.;T;T;T;T;T;T;T;T;T
M_CAP
Benign
T
MetaRNN
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Benign
T
MutationTaster
Benign
D;D;D;D;D;D
PrimateAI
Uncertain
T
Sift4G
Benign
T;T;T;T;T;T;T;T;T;T;T;T;T;T
Polyphen
0.010
.;B;.;.;.;.;.;.;B;.;.;.;.;.
Vest4
MVP
MPC
0.37
ClinPred
T
GERP RS
RBP_binding_hub_radar
RBP_regulation_power_radar
Varity_R
gMVP
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at