10-5785933-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001494.4(GDI2):​c.506G>A​(p.Arg169Gln) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.000031 in 1,610,544 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000085 ( 0 hom., cov: 32)
Exomes 𝑓: 0.000025 ( 0 hom. )

Consequence

GDI2
NM_001494.4 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 7.79
Variant links:
Genes affected
GDI2 (HGNC:4227): (GDP dissociation inhibitor 2) GDP dissociation inhibitors are proteins that regulate the GDP-GTP exchange reaction of members of the rab family, small GTP-binding proteins of the ras superfamily, that are involved in vesicular trafficking of molecules between cellular organelles. GDIs slow the rate of dissociation of GDP from rab proteins and release GDP from membrane-bound rabs. GDI2 is ubiquitously expressed. The GDI2 gene contains many repetitive elements indicating that it may be prone to inversion/deletion rearrangements. Alternative splicing results in multiple transcript variants encoding distinct isoforms. [provided by RefSeq, Jul 2008]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.10590777).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GDI2NM_001494.4 linkc.506G>A p.Arg169Gln missense_variant Exon 5 of 11 ENST00000380191.9 NP_001485.2 P50395-1Q6IAT1
GDI2NM_001115156.2 linkc.371G>A p.Arg124Gln missense_variant Exon 4 of 10 NP_001108628.1 P50395-2Q6IAT1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GDI2ENST00000380191.9 linkc.506G>A p.Arg169Gln missense_variant Exon 5 of 11 1 NM_001494.4 ENSP00000369538.4 P50395-1

Frequencies

GnomAD3 genomes
AF:
0.0000854
AC:
13
AN:
152172
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000290
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000147
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000438
AC:
11
AN:
251416
Hom.:
0
AF XY:
0.0000515
AC XY:
7
AN XY:
135886
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.0000289
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000131
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000254
AC:
37
AN:
1458254
Hom.:
0
Cov.:
29
AF XY:
0.0000262
AC XY:
19
AN XY:
725740
show subpopulations
Gnomad4 AFR exome
AF:
0.000449
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000104
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000631
Gnomad4 OTH exome
AF:
0.0000497
GnomAD4 genome
AF:
0.0000854
AC:
13
AN:
152290
Hom.:
0
Cov.:
32
AF XY:
0.0000806
AC XY:
6
AN XY:
74468
show subpopulations
Gnomad4 AFR
AF:
0.000289
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000147
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000127
Hom.:
0
Bravo
AF:
0.0000793
ExAC
AF:
0.0000824
AC:
10
Asia WGS
AF:
0.000289
AC:
1
AN:
3478
EpiCase
AF:
0.0000545
EpiControl
AF:
0.00

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Feb 25, 2025
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.506G>A (p.R169Q) alteration is located in exon 5 (coding exon 5) of the GDI2 gene. This alteration results from a G to A substitution at nucleotide position 506, causing the arginine (R) at amino acid position 169 to be replaced by a glutamine (Q). 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
0.19
BayesDel_addAF
Benign
-0.076
T
BayesDel_noAF
Uncertain
-0.030
CADD
Uncertain
24
DANN
Uncertain
0.97
DEOGEN2
Benign
0.31
T;.;.;.
Eigen
Benign
-0.021
Eigen_PC
Benign
0.14
FATHMM_MKL
Pathogenic
0.99
D
LIST_S2
Uncertain
0.96
D;D;D;D
M_CAP
Benign
0.011
T
MetaRNN
Benign
0.11
T;T;T;T
MetaSVM
Benign
-0.95
T
MutationAssessor
Benign
1.3
L;.;.;.
PrimateAI
Uncertain
0.57
T
PROVEAN
Benign
-0.090
N;N;N;N
REVEL
Benign
0.19
Sift
Benign
0.42
T;T;T;T
Sift4G
Benign
0.41
T;T;T;T
Polyphen
0.014
B;.;.;.
Vest4
0.79
MVP
0.86
MPC
0.41
ClinPred
0.11
T
GERP RS
5.4
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.7
Varity_R
0.067
gMVP
0.75

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: rs530025524; hg19: chr10-5827896; API