2-127651063-CTC-GTG

Variant names:

• chr2-127651063-CTC-GTG
• NM_001161417.2:c.328_330delCTCinsGTG
• GPR17 p.Leu110Val

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 0P and 0B.

The NM_001161417.2(GPR17):​c.328_330delCTCinsGTG​(p.Leu110Val) variant causes a missense change. The variant was absent in control chromosomes in GnomAD project. It is difficult to determine the true allele frequency of this variant because it is of type MNV, and the frequency of such variant types in population databases may be underestimated and unreliable. 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)
• Consequence: GPR17 NM_001161417.2 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.25
• Publications: 0 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: Unknown, AR Classification: SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, Ambry Genetics
• autosomal recessive limb-girdle muscular dystrophy

  Inheritance: AR Classification: NO_KNOWN Submitted by: ClinGen

ACMG classification

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

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

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR17	NM_001161417.2	MANE Select	c.328_330delCTCinsGTG	p.Leu110Val	missense	N/A	NP_001154889.1	Q13304-2
	LIMS2	NM_001161403.3	MANE Select	c.359+3359_359+3361delGAGinsCAC		intron	N/A	NP_001154875.1	Q7Z4I7-1
	GPR17	NM_001161415.2		c.412_414delCTCinsGTG	p.Leu138Val	missense	N/A	NP_001154887.1	Q13304-1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	GPR17	ENST00000486700.2	TSL:1 MANE Select	c.328_330delCTCinsGTG	p.Leu110Val	missense	N/A	ENSP00000508383.1	Q13304-2
	GPR17	ENST00000272644.7	TSL:1	c.412_414delCTCinsGTG	p.Leu138Val	missense	N/A	ENSP00000272644.3	Q13304-1
	GPR17	ENST00000393018.3	TSL:1	c.412_414delCTCinsGTG	p.Leu138Val	missense	N/A	ENSP00000376741.3	Q13304-1

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		6.2

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

hg19: chr2-128408637;