NM_001103146.3:c.110A>G

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001103146.3(GIGYF2):ā€‹c.110A>Gā€‹(p.Lys37Arg) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,624 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (ā˜…).

Frequency

Genomes: not found (cov: 32)
Exomes š‘“: 6.8e-7 ( 0 hom. )

Consequence

GIGYF2
NM_001103146.3 missense

Scores

4
8
6

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.46
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]

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GIGYF2NM_001103146.3 linkc.110A>G p.Lys37Arg missense_variant Exon 4 of 29 ENST00000373563.9 NP_001096616.1 Q6Y7W6-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GIGYF2ENST00000373563.9 linkc.110A>G p.Lys37Arg missense_variant Exon 4 of 29 1 NM_001103146.3 ENSP00000362664.5 Q6Y7W6-1

Frequencies

GnomAD3 genomes
Cov.:
32
GnomAD4 exome
AF:
6.84e-7
AC:
1
AN:
1461624
Hom.:
0
Cov.:
31
AF XY:
0.00
AC XY:
0
AN XY:
727130
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
8.99e-7
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
32

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Nov 08, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.110A>G (p.K37R) 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 110, causing the lysine (K) at amino acid position 37 to be replaced by an arginine (R). 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
0.18
BayesDel_addAF
Uncertain
0.094
D
BayesDel_noAF
Benign
-0.10
CADD
Uncertain
24
DANN
Uncertain
1.0
DEOGEN2
Benign
0.22
.;T;T;T;.;.;.;.;T;T;.;.;T;T
Eigen
Pathogenic
0.72
Eigen_PC
Pathogenic
0.72
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Pathogenic
0.99
D;.;D;D;.;D;D;D;D;D;D;D;D;D
M_CAP
Benign
0.030
D
MetaRNN
Uncertain
0.48
T;T;T;T;T;T;T;T;T;T;T;T;T;T
MetaSVM
Uncertain
0.25
D
PrimateAI
Uncertain
0.78
T
PROVEAN
Benign
-2.2
.;N;D;D;N;D;D;D;N;N;N;N;D;N
REVEL
Uncertain
0.36
Sift
Uncertain
0.014
.;D;T;.;D;D;T;T;D;D;D;D;T;D
Sift4G
Uncertain
0.023
D;D;T;D;D;T;T;T;D;D;D;D;T;D
Polyphen
0.95
.;P;.;.;.;.;.;.;P;.;.;.;.;.
Vest4
0.70
MutPred
0.21
Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);Loss of ubiquitination at K37 (P = 0.0148);
MVP
0.81
MPC
0.92
ClinPred
0.95
D
GERP RS
5.8
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1
Varity_R
0.65
gMVP
0.86

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr2-233612393; API