2-127651169-C-T

Variant summary

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

The NM_001161417.2(GPR17):​c.434C>T​(p.Pro145Leu) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,460,300 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: not found (cov: 33)
Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

GPR17
NM_001161417.2 missense

Scores

6
13

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.09
Variant links:
Genes affected
GPR17 (HGNC:4471): (G protein-coupled receptor 17) Predicted to enable G protein-coupled receptor activity. Predicted to be involved in positive regulation of Rho protein signal transduction and positive regulation of cytosolic calcium ion concentration involved in phospholipase C-activating G protein-coupled signaling pathway. Predicted to act upstream of or within negative regulation of inflammatory response to antigenic stimulus. Predicted to be located in plasma membrane. Predicted to be integral component of plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]
LIMS2 (HGNC:16084): (LIM zinc finger domain containing 2) This gene encodes a member of a small family of focal adhesion proteins which interacts with ILK (integrin-linked kinase), a protein which effects protein-protein interactions with the extraceullar matrix. The encoded protein has five LIM domains, each domain forming two zinc fingers, which permit interactions which regulate cell shape and migration. A pseudogene of this gene is located on chromosome 4. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Nov 2011]

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=0.26246998).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR17NM_001161417.2 linkc.434C>T p.Pro145Leu missense_variant Exon 2 of 2 ENST00000486700.2 NP_001154889.1 Q13304-2G4XH68
LIMS2NM_001161403.3 linkc.359+3255G>A intron_variant Intron 4 of 9 ENST00000355119.9 NP_001154875.1 Q7Z4I7-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
GPR17ENST00000486700.2 linkc.434C>T p.Pro145Leu missense_variant Exon 2 of 2 1 NM_001161417.2 ENSP00000508383.1 Q13304-2
LIMS2ENST00000355119.9 linkc.359+3255G>A intron_variant Intron 4 of 9 1 NM_001161403.3 ENSP00000347240.4 Q7Z4I7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD3 exomes
AF:
0.00000399
AC:
1
AN:
250330
Hom.:
0
AF XY:
0.00000738
AC XY:
1
AN XY:
135464
show subpopulations
Gnomad AFR exome
AF:
0.00
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.00
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.00000881
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1460300
Hom.:
0
Cov.:
31
AF XY:
0.00000275
AC XY:
2
AN XY:
726500
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:
0.00000180
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

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

Submissions by phenotype

not specified Uncertain:1
Dec 25, 2024
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.518C>T (p.P173L) alteration is located in exon 4 (coding exon 2) of the GPR17 gene. This alteration results from a C to T substitution at nucleotide position 518, causing the proline (P) at amino acid position 173 to be replaced by a leucine (L). 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
0.31
BayesDel_addAF
Uncertain
0.018
T
BayesDel_noAF
Benign
-0.21
CADD
Uncertain
23
DANN
Uncertain
0.99
DEOGEN2
Benign
0.084
T;T;T
Eigen
Benign
0.077
Eigen_PC
Uncertain
0.26
FATHMM_MKL
Uncertain
0.95
D
LIST_S2
Uncertain
0.92
D;.;.
M_CAP
Benign
0.063
D
MetaRNN
Benign
0.26
T;T;T
MetaSVM
Benign
-0.77
T
MutationAssessor
Benign
1.6
L;L;L
PrimateAI
Uncertain
0.52
T
PROVEAN
Benign
-1.3
N;N;N
REVEL
Benign
0.18
Sift
Benign
0.075
T;T;T
Sift4G
Benign
0.39
T;T;T
Polyphen
0.14
B;B;B
Vest4
0.26
MutPred
0.61
Loss of glycosylation at P173 (P = 0.053);Loss of glycosylation at P173 (P = 0.053);Loss of glycosylation at P173 (P = 0.053);
MVP
0.68
MPC
0.32
ClinPred
0.58
D
GERP RS
5.5
Varity_R
0.28
gMVP
0.53

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: rs1368566676; hg19: chr2-128408743; API