rs13021001

Variant names:

• chr2-127651845-A-G
• rs13021001
• NM_001161417.2:c.*90A>G

Variant summary

Our verdict is Benign. The variant received -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
• Publications: 13 publications found

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]

LIMS2 Gene-Disease associations (from GenCC):

• autosomal recessive limb-girdle muscular dystrophy type 2W

  Inheritance: AR, Unknown Classification: SUPPORTIVE, LIMITED Submitted by: Orphanet, Ambry Genetics, Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -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.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001161417.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR17	NM_001161417.2	MANE Select	c.*90A>G		3_prime_UTR	Exon 2 of 2	NP_001154889.1
	LIMS2	NM_001161403.3	MANE Select	c.359+2579T>C		intron	N/A	NP_001154875.1
	GPR17	NM_001161415.2		c.*90A>G		3_prime_UTR	Exon 4 of 4	NP_001154887.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR17	ENST00000486700.2	TSL:1 MANE Select	c.*90A>G		3_prime_UTR	Exon 2 of 2	ENSP00000508383.1
	GPR17	ENST00000272644.7	TSL:1	c.*90A>G		3_prime_UTR	Exon 3 of 3	ENSP00000272644.3
	LIMS2	ENST00000355119.9	TSL:1 MANE Select	c.359+2579T>C		intron	N/A	ENSP00000347240.4

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

African (AFR) AF: 0.0385 AC: 966 AN: 25100

American (AMR) AF: 0.0845 AC: 2619 AN: 31004

Ashkenazi Jewish (ASJ) AF: 0.147 AC: 2761 AN: 18846

East Asian (EAS) AF: 0.157 AC: 5786 AN: 36798

South Asian (SAS) AF: 0.233 AC: 15302 AN: 65648

European-Finnish (FIN) AF: 0.101 AC: 4886 AN: 48276

Middle Eastern (MID) AF: 0.192 AC: 641 AN: 3332

European-Non Finnish (NFE) AF: 0.128 AC: 102633 AN: 804812

Other (OTH) AF: 0.136 AC: 6344 AN: 46624

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

African (AFR) AF: 0.0413 AC: 1717 AN: 41570

American (AMR) AF: 0.125 AC: 1917 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.154 AC: 535 AN: 3470

East Asian (EAS) AF: 0.165 AC: 858 AN: 5186

South Asian (SAS) AF: 0.238 AC: 1149 AN: 4820

European-Finnish (FIN) AF: 0.0967 AC: 1025 AN: 10602

Middle Eastern (MID) AF: 0.146 AC: 43 AN: 294

European-Non Finnish (NFE) AF: 0.131 AC: 8901 AN: 67992

Other (OTH) AF: 0.136 AC: 287 AN: 2110

Alfa AF: 0.131 Hom.: 2937

Bravo AF: 0.105

Asia WGS AF: 0.190 AC: 661 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.84
CADD	Benign	4.0
DANN	Benign	0.47
PhyloP100		0.78
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

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