Genetic Variant FPR2:p.Pro213Leu (chr19-51769296-C-T) – ACMG Classification: Uncertain_significance (3 pts)

Variant summary

Our verdict is Uncertain significance. Variant got 3 ACMG points: 3P and 0B. PM2PP3

The NM_001005738.2(FPR2):c.638C>T(p.Pro213Leu) variant causes a missense change. The variant allele was found at a frequency of 0.0000223 in 1,614,168 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.00011 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

FPR2
NM_001005738.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 5.56

Variant links:

Genes affected

FPR2 (HGNC:3827): (formyl peptide receptor 2) Enables amyloid-beta binding activity; scavenger receptor binding activity; and signaling receptor activity. Involved in several processes, including cellular response to amyloid-beta; positive regulation of monocyte chemotaxis; and regulation of defense response. Located in cytoplasm and plasma membrane. [provided by Alliance of Genome Resources, Apr 2022]

FPR2 links:

FPR1 (HGNC:3826): (formyl peptide receptor 1) This gene encodes a G protein-coupled receptor of mammalian phagocytic cells that is a member of the G-protein coupled receptor 1 family. The protein mediates the response of phagocytic cells to invasion of the host by microorganisms and is important in host defense and inflammation.[provided by RefSeq, Jul 2010]

FPR1 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 3 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.75

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FPR2	NM_001005738.2 link	c.638C>T	p.Pro213Leu	missense_variant	Exon 2 of 2	ENST00000340023.7	NP_001005738.1	P25090A0A024R4P3
FPR2	NM_001462.3 link	c.638C>T	p.Pro213Leu	missense_variant	Exon 2 of 2		NP_001453.1	P25090A0A024R4P3
FPR2	XM_006723120.4 link	c.638C>T	p.Pro213Leu	missense_variant	Exon 3 of 3		XP_006723183.1	P25090A0A024R4P3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPR2	ENST00000340023.7 link	c.638C>T	p.Pro213Leu	missense_variant	Exon 2 of 2	1	NM_001005738.2	ENSP00000340191.4		P25090

Frequencies

GnomAD3 genomes

AF:

0.000112

AC:

AN:

152156

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000386

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.0000557

AC:

AN:

251484

Hom.:

AF XY:

0.0000441

AC XY:

AN XY:

135918

show subpopulations

Gnomad AFR exome

AF:

0.000492

Gnomad AMR exome

AF:

0.0000578

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.0000653

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000879

Gnomad OTH exome

AF:

0.000163

GnomAD4 exome

AF:

0.0000130

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.0000138

AC XY:

AN XY:

727248

show subpopulations

Gnomad4 AFR exome

AF:

0.000358

Gnomad4 AMR exome

AF:

0.0000447

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.0000232

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

8.99e-7

Gnomad4 OTH exome

AF:

0.0000166

GnomAD4 genome

AF:

0.000112

AC:

AN:

152274

Hom.:

Cov.:

AF XY:

0.0000940

AC XY:

AN XY:

74468

show subpopulations

Gnomad4 AFR

AF:

0.000385

Gnomad4 AMR

AF:

0.0000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000935

Hom.:

Bravo

AF:

0.000110

ESP6500AA

AF:

0.000908

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.0000659

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Mar 01, 2023

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.638C>T (p.P213L) alteration is located in exon 2 (coding exon 1) of the FPR2 gene. This alteration results from a C to T substitution at nucleotide position 638, causing the proline (P) at amino acid position 213 to be replaced by a leucine (L). Based on insufficient or conflicting evidence, the clinical significance of this alteration remains unclear. -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.78

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.16

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Uncertain

0.44

T;T;T

Eigen

Uncertain

0.52

Eigen_PC

Uncertain

0.26

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.88

.;.;D

M_CAP

Benign

0.024

MetaRNN

Pathogenic

0.75

D;D;D

MetaSVM

Uncertain

0.24

MutationAssessor

Pathogenic

4.5

H;H;H

PrimateAI

Benign

0.43

PROVEAN

Pathogenic

-9.6

D;.;.

REVEL

Uncertain

0.39

Sift

Pathogenic

0.0

D;.;.

Sift4G

Pathogenic

0.0

D;D;D

Polyphen

1.0

D;D;D

Vest4

0.59

MVP

0.70

MPC

0.94

ClinPred

0.99

GERP RS

3.8

Varity_R

0.81

gMVP

0.71

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over