2-127650780-C-A

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_001161417.2(GPR17):c.45C>A(p.Phe15Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00427 in 1,613,876 control chromosomes in the GnomAD database, including 18 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

Frequency

Genomes: 𝑓 0.0028 ( 0 hom., cov: 33)

Exomes 𝑓: 0.0044 ( 18 hom. )

Consequence

GPR17
NM_001161417.2 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: 0.184

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]

GPR17 links:

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]

LIMS2 links:

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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=0.0051125884).

BP6

Variant 2-127650780-C-A is Benign according to our data. Variant chr2-127650780-C-A is described in ClinVar as [Likely_benign]. Clinvar id is 3770656.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome4 at 18 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
GPR17	NM_001161417.2 link	c.45C>A	p.Phe15Leu	missense_variant	Exon 2 of 2	ENST00000486700.2	NP_001154889.1	Q13304-2G4XH68
LIMS2	NM_001161403.3 link	c.359+3644G>T		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
GPR17	ENST00000486700.2 link	c.45C>A	p.Phe15Leu	missense_variant	Exon 2 of 2	1	NM_001161417.2	ENSP00000508383.1		Q13304-2
LIMS2	ENST00000355119.9 link	c.359+3644G>T		intron_variant	Intron 4 of 9	1	NM_001161403.3	ENSP00000347240.4		Q7Z4I7-1

Frequencies

GnomAD3 genomes

AF:

0.00276

AC:

420

AN:

152266

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00123

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00275

Gnomad ASJ

AF:

0.000865

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000188

Gnomad MID

AF:

0.0127

Gnomad NFE

AF:

0.00463

Gnomad OTH

AF:

0.00143

GnomAD3 exomes

AF:

0.00228

AC:

566

AN:

248540

Hom.:

AF XY:

0.00217

AC XY:

293

AN XY:

134746

show subpopulations

Gnomad AFR exome

AF:

0.000987

Gnomad AMR exome

AF:

0.00159

Gnomad ASJ exome

AF:

0.000498

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.000879

Gnomad NFE exome

AF:

0.00414

Gnomad OTH exome

AF:

0.00164

GnomAD4 exome

AF:

0.00443

AC:

6470

AN:

1461492

Hom.:

Cov.:

AF XY:

0.00427

AC XY:

3104

AN XY:

727040

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00179

Gnomad4 ASJ exome

AF:

0.000268

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000464

Gnomad4 FIN exome

AF:

0.000882

Gnomad4 NFE exome

AF:

0.00541

Gnomad4 OTH exome

AF:

0.00459

GnomAD4 genome

AF:

0.00276

AC:

420

AN:

152384

Hom.:

Cov.:

AF XY:

0.00272

AC XY:

203

AN XY:

74518

show subpopulations

Gnomad4 AFR

AF:

0.00123

Gnomad4 AMR

AF:

0.00274

Gnomad4 ASJ

AF:

0.000865

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000188

Gnomad4 NFE

AF:

0.00463

Gnomad4 OTH

AF:

0.00142

Alfa

AF:

0.00422

Hom.:

Bravo

AF:

0.00286

TwinsUK

AF:

0.00485

AC:

ALSPAC

AF:

0.00727

AC:

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00372

AC:

ExAC

AF:

0.00241

AC:

293

Asia WGS

AF:

0.000866

AC:

AN:

3478

EpiCase

AF:

0.00371

EpiControl

AF:

0.00427

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Dec 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

GPR17: BP4, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.25

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

CADD

Benign

0.74

DANN

Benign

0.60

DEOGEN2

Benign

0.057

T;T;.;T

Eigen

Benign

-1.0

Eigen_PC

Benign

-0.94

FATHMM_MKL

Benign

0.34

LIST_S2

Benign

0.23

T;.;T;.

M_CAP

Benign

0.013

MetaRNN

Benign

0.0051

T;T;T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.0

N;N;.;N

PrimateAI

Benign

0.29

PROVEAN

Benign

0.12

N;N;N;N

REVEL

Benign

0.088

Sift

Benign

0.61

T;T;T;T

Sift4G

Benign

0.81

T;T;T;T

Polyphen

0.0

B;B;.;B

Vest4

0.055

MutPred

0.34

Gain of disorder (P = 0.0878);Gain of disorder (P = 0.0878);Gain of disorder (P = 0.0878);Gain of disorder (P = 0.0878);

MVP

0.34

MPC

0.29

ClinPred

0.0035

GERP RS

1.3

Varity_R

0.042

gMVP

0.17

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over