rs762516436

Variant names:

• chr2-127650763-G-A
• rs762516436
• NM_001161417.2:c.28G>A

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 2P and 6B. PM2 BP4_Strong BP6_Moderate

The NM_001161417.2(GPR17):​c.28G>A​(p.Gly10Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000411 in 1,461,444 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 17/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 0.0000041 (0 hom.)
• Consequence: GPR17 NM_001161417.2 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0160
• 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: Likely_benign. The variant received -4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.03545925).
• BP6: Variant 2-127650763-G-A is Benign according to our data. Variant chr2-127650763-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 3855226.Status of the report is criteria_provided_single_submitter, 1 stars.

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.28G>A	p.Gly10Ser	missense	Exon 2 of 2	NP_001154889.1	Q13304-2
	LIMS2	NM_001161403.3	MANE Select	c.359+3661C>T		intron	N/A	NP_001154875.1	Q7Z4I7-1
	GPR17	NM_001161415.2		c.112G>A	p.Gly38Ser	missense	Exon 4 of 4	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.28G>A	p.Gly10Ser	missense	Exon 2 of 2	ENSP00000508383.1	Q13304-2
	GPR17	ENST00000272644.7	TSL:1	c.112G>A	p.Gly38Ser	missense	Exon 3 of 3	ENSP00000272644.3	Q13304-1
	GPR17	ENST00000393018.3	TSL:1	c.112G>A	p.Gly38Ser	missense	Exon 2 of 2	ENSP00000376741.3	Q13304-1

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD2 exomes AF: 0.00000402 AC: 1 AN: 248754 AF XY: 0.00

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000411 AC: 6 AN: 1461444 Hom.: 0 Cov.: 30 AF XY: 0.00000275 AC XY: 2 AN XY: 727036

African (AFR) AF: 0.00 AC: 0 AN: 33466

American (AMR) AF: 0.00 AC: 0 AN: 44702

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000756 AC: 3 AN: 39694

South Asian (SAS) AF: 0.00 AC: 0 AN: 86244

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53238

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5766

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1111816

Other (OTH) AF: 0.0000497 AC: 3 AN: 60382

GnomAD4 genome Cov.: 33

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ExAC AF: 0.00000824 AC: 1

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.29	T
BayesDel_noAF	Benign	-0.48
CADD	Benign	0.20
DANN	Benign	0.57
DEOGEN2	Benign	0.053	T
Eigen	Benign	-1.1
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.046	N
LIST_S2	Benign	0.45	T
M_CAP	Benign	0.0087	T
MetaRNN	Benign	0.035	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	-0.34	N
PhyloP100		-0.016
PrimateAI	Benign	0.23	T
PROVEAN	Benign	-0.18	N
REVEL	Benign	0.099
Sift	Benign	0.83	T
Sift4G	Benign	0.81	T
Polyphen		0.0010	B
Vest4		0.041
MVP		0.067
MPC		0.25
ClinPred		0.042	T
GERP RS		0.54
PromoterAI		0.014	Neutral
Varity_R		0.033
gMVP		0.11
Mutation Taster		=99/1	polymorphism

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: rs762516436; hg19: chr2-128408337;