chr2-127651063-C-G

Variant summary

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

The NM_001161417.2(GPR17):​c.328C>G​(p.Leu110Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,408 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. L110F) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 33)
Exomes š‘“: 0.0000014 ( 0 hom. )

Consequence

GPR17
NM_001161417.2 missense

Scores

1
18

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.638
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]

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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=0.25770962).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
GPR17NM_001161417.2 linkc.328C>G p.Leu110Val missense_variant Exon 2 of 2 ENST00000486700.2 NP_001154889.1 Q13304-2G4XH68
LIMS2NM_001161403.3 linkc.359+3361G>C 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.328C>G p.Leu110Val missense_variant Exon 2 of 2 1 NM_001161417.2 ENSP00000508383.1 Q13304-2
LIMS2ENST00000355119.9 linkc.359+3361G>C intron_variant Intron 4 of 9 1 NM_001161403.3 ENSP00000347240.4 Q7Z4I7-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000137
AC:
2
AN:
1461408
Hom.:
0
Cov.:
32
AF XY:
0.00000138
AC XY:
1
AN XY:
726992
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

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.19
BayesDel_addAF
Benign
-0.17
T
BayesDel_noAF
Benign
-0.49
CADD
Benign
16
DANN
Benign
0.97
DEOGEN2
Benign
0.068
T;T;T
Eigen
Benign
-0.14
Eigen_PC
Benign
-0.089
FATHMM_MKL
Benign
0.73
D
LIST_S2
Benign
0.81
T;.;.
M_CAP
Benign
0.015
T
MetaRNN
Benign
0.26
T;T;T
MetaSVM
Benign
-1.1
T
MutationAssessor
Benign
1.7
L;L;L
PrimateAI
Uncertain
0.60
T
PROVEAN
Benign
-1.0
N;N;N
REVEL
Benign
0.069
Sift
Benign
0.062
T;T;T
Sift4G
Benign
0.19
T;T;T
Polyphen
0.67
P;P;P
Vest4
0.20
MutPred
0.53
Gain of methylation at R133 (P = 0.1518);Gain of methylation at R133 (P = 0.1518);Gain of methylation at R133 (P = 0.1518);
MVP
0.46
MPC
0.40
ClinPred
0.33
T
GERP RS
1.6
Varity_R
0.13
gMVP
0.36

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: chr2-128408637; API