chr2-127650815-C-T

Position:

• chr2-127650815-C-T

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP4_Strong BP6_Very_Strong BS2

The NM_001161417.2(GPR17):​c.80C>T​(p.Thr27Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000681 in 1,613,700 control chromosomes in the GnomAD database, including 7 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.0036 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00038 (3 hom.)
• Consequence: GPR17 NM_001161417.2 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.93

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 -16 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.0048942566).
• BP6: Variant 2-127650815-C-T is Benign according to our data. Variant chr2-127650815-C-T is described in ClinVar as [Benign]. Clinvar id is 785852.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
GPR17	NM_001161417.2	c.80C>T	p.Thr27Met	missense_variant	2/2	ENST00000486700.2
LIMS2	NM_001161403.3	c.359+3609G>A		intron_variant		ENST00000355119.9

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
GPR17	ENST00000486700.2	c.80C>T	p.Thr27Met	missense_variant	2/2	1	NM_001161417.2	P1
LIMS2	ENST00000355119.9	c.359+3609G>A		intron_variant		1	NM_001161403.3	P1

Frequencies

GnomAD3 genomes AF: 0.00360 AC: 548 AN: 152250 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0116

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00340

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000769

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000441

Gnomad OTH AF: 0.00478

GnomAD3 exomes AF: 0.00101 AC: 252 AN: 249046 Hom.: 0 AF XY: 0.000682 AC XY: 92 AN XY: 134844

Gnomad AFR exome AF: 0.0127

Gnomad AMR exome AF: 0.000665

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000598

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000539

Gnomad OTH exome AF: 0.000817

GnomAD4 exome AF: 0.000378 AC: 553 AN: 1461332 Hom.: 3 Cov.: 31 AF XY: 0.000338 AC XY: 246 AN XY: 726970

Gnomad4 AFR exome AF: 0.0109

Gnomad4 AMR exome AF: 0.000850

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000529

Gnomad4 SAS exome AF: 0.0000464

Gnomad4 FIN exome AF: 0.0000187

Gnomad4 NFE exome AF: 0.0000459

Gnomad4 OTH exome AF: 0.00106

GnomAD4 genome AF: 0.00358 AC: 546 AN: 152368 Hom.: 4 Cov.: 33 AF XY: 0.00348 AC XY: 259 AN XY: 74506

Gnomad4 AFR AF: 0.0115

Gnomad4 AMR AF: 0.00340

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000771

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00473

Alfa AF: 0.000626 Hom.: 0

Bravo AF: 0.00417

ESP6500AA AF: 0.0111 AC: 49

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00128 AC: 155

Asia WGS AF: 0.000866 AC: 3 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 13, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.15
BayesDel_addAF	Benign	-0.42	T
BayesDel_noAF	Benign	-0.37
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.11	T;T;.;T
Eigen	Uncertain	0.45
Eigen_PC	Uncertain	0.50
FATHMM_MKL	Uncertain	0.95	D
LIST_S2	Uncertain	0.89	D;.;D;.
MetaRNN	Benign	0.0049	T;T;T;T
MetaSVM	Benign	-0.89	T
MutationAssessor	Benign	0.90	L;L;.;L
MutationTaster	Benign	1.0	D;D;D;D;D;D;D;D;D;D
PrimateAI	Uncertain	0.50	T
PROVEAN	Benign	-1.5	N;N;N;N
REVEL	Benign	0.24
Sift	Benign	0.036	D;D;T;D
Sift4G	Uncertain	0.060	T;T;T;T
Polyphen		1.0	D;D;.;D
Vest4		0.62
MVP		0.44
MPC		0.41
ClinPred		0.034	T
GERP RS		5.2
Varity_R		0.073
gMVP		0.33

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: rs61738377; hg19: chr2-128408389;