rs13021001

Positions:

• chr2-127651845-A-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001161417.2(GPR17):​c.*90A>G variant causes a 3 prime UTR change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.129 in 1,232,696 control chromosomes in the GnomAD database, including 11,414 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.11 (1114 hom., cov: 33)
  • Exomes 𝑓: 0.13 (10300 hom.)
• Consequence: GPR17 NM_001161417.2 3_prime_UTR
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.779

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.84).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.227 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR17	NM_001161417.2	c.*90A>G		3_prime_UTR_variant	2/2	ENST00000486700.2	NP_001154889.1
LIMS2	NM_001161403.3	c.359+2579T>C		intron_variant		ENST00000355119.9	NP_001154875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR17	ENST00000486700.2	c.*90A>G		3_prime_UTR_variant	2/2	1	NM_001161417.2	ENSP00000508383	P1
LIMS2	ENST00000355119.9	c.359+2579T>C		intron_variant		1	NM_001161403.3	ENSP00000347240	P1

Frequencies

GnomAD3 genomes AF: 0.110 AC: 16661 AN: 152138 Hom.: 1114 Cov.: 33

Gnomad AFR AF: 0.0413

Gnomad AMI AF: 0.265

Gnomad AMR AF: 0.125

Gnomad ASJ AF: 0.154

Gnomad EAS AF: 0.166

Gnomad SAS AF: 0.238

Gnomad FIN AF: 0.0967

Gnomad MID AF: 0.139

Gnomad NFE AF: 0.131

Gnomad OTH AF: 0.132

GnomAD4 exome AF: 0.131 AC: 141938 AN: 1080440 Hom.: 10300 Cov.: 14 AF XY: 0.135 AC XY: 72869 AN XY: 539544

Gnomad4 AFR exome AF: 0.0385

Gnomad4 AMR exome AF: 0.0845

Gnomad4 ASJ exome AF: 0.147

Gnomad4 EAS exome AF: 0.157

Gnomad4 SAS exome AF: 0.233

Gnomad4 FIN exome AF: 0.101

Gnomad4 NFE exome AF: 0.128

Gnomad4 OTH exome AF: 0.136

GnomAD4 genome AF: 0.110 AC: 16674 AN: 152256 Hom.: 1114 Cov.: 33 AF XY: 0.110 AC XY: 8219 AN XY: 74450

Gnomad4 AFR AF: 0.0413

Gnomad4 AMR AF: 0.125

Gnomad4 ASJ AF: 0.154

Gnomad4 EAS AF: 0.165

Gnomad4 SAS AF: 0.238

Gnomad4 FIN AF: 0.0967

Gnomad4 NFE AF: 0.131

Gnomad4 OTH AF: 0.136

Alfa AF: 0.134 Hom.: 2225

Bravo AF: 0.105

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.47

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

Other links and lift over

dbSNP: rs13021001; hg19: chr2-128409419; COSMIC: COSV55757326; COSMIC: COSV55757326;