chr2-127651269-G-A

Position:

• chr2-127651269-G-A

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_Strong BP6_Very_Strong BP7 BA1

The NM_001161417.2(GPR17):​c.534G>A​(p.Thr178Thr) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00403 in 1,606,540 control chromosomes in the GnomAD database, including 213 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.021 (123 hom., cov: 33)
  • Exomes 𝑓: 0.0022 (90 hom.)
• Consequence: GPR17 NM_001161417.2 synonymous
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: -3.97

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]

GPR17 (HGNC:):

ACMG classification

Verdict is Benign. Variant got -21 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.79).
• BP6: Variant 2-127651269-G-A is Benign according to our data. Variant chr2-127651269-G-A is described in ClinVar as [Benign]. Clinvar id is 785853.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BP7: Synonymous conserved (PhyloP=-3.97 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0695 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
GPR17	NM_001161417.2	c.534G>A	p.Thr178Thr	synonymous_variant	2/2	ENST00000486700.2	NP_001154889.1
LIMS2	NM_001161403.3	c.359+3155C>T		intron_variant		ENST00000355119.9	NP_001154875.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
GPR17	ENST00000486700.2	c.534G>A	p.Thr178Thr	synonymous_variant	2/2	1	NM_001161417.2	ENSP00000508383.1
LIMS2	ENST00000355119.9	c.359+3155C>T		intron_variant		1	NM_001161403.3	ENSP00000347240.4

Frequencies

GnomAD3 genomes AF: 0.0212 AC: 3221 AN: 152168 Hom.: 123 Cov.: 33

Gnomad AFR AF: 0.0717

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0120

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.0000942

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000309

Gnomad OTH AF: 0.0201

GnomAD3 exomes AF: 0.00561 AC: 1376 AN: 245358 Hom.: 53 AF XY: 0.00429 AC XY: 571 AN XY: 133198

Gnomad AFR exome AF: 0.0730

Gnomad AMR exome AF: 0.00394

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.000164

Gnomad FIN exome AF: 0.0000586

Gnomad NFE exome AF: 0.000328

Gnomad OTH exome AF: 0.00231

GnomAD4 exome AF: 0.00223 AC: 3240 AN: 1454254 Hom.: 90 Cov.: 32 AF XY: 0.00197 AC XY: 1424 AN XY: 723634

Gnomad4 AFR exome AF: 0.0713

Gnomad4 AMR exome AF: 0.00465

Gnomad4 ASJ exome AF: 0.0000384

Gnomad4 EAS exome AF: 0.000101

Gnomad4 SAS exome AF: 0.000209

Gnomad4 FIN exome AF: 0.0000429

Gnomad4 NFE exome AF: 0.000284

Gnomad4 OTH exome AF: 0.00471

GnomAD4 genome AF: 0.0212 AC: 3229 AN: 152286 Hom.: 123 Cov.: 33 AF XY: 0.0200 AC XY: 1493 AN XY: 74466

Gnomad4 AFR AF: 0.0717

Gnomad4 AMR AF: 0.0120

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000207

Gnomad4 FIN AF: 0.0000942

Gnomad4 NFE AF: 0.000309

Gnomad4 OTH AF: 0.0199

Alfa AF: 0.0111 Hom.: 31

Bravo AF: 0.0245

Asia WGS AF: 0.00491 AC: 17 AN: 3478

EpiCase AF: 0.000491

EpiControl AF: 0.000296

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 13, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.79
CADD	Benign	0.013
DANN	Benign	0.67

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: rs6708099; hg19: chr2-128408843;