Genetic Variant FPR2:p.Pro213Gln (chr19-51769296-C-A) – ACMG Classification: Likely_pathogenic (6 pts)

Variant summary

Our verdict is Likely pathogenic. The variant received 6 ACMG points: 6P and 0B. PM2PP3_Strong

The NM_001005738.2(FPR2):c.638C>A(p.Pro213Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00000137 in 1,461,894 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic outcome for this variant. 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. P213L) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Exomes 𝑓: 0.0000014 ( 0 hom. )

Consequence

FPR2
NM_001005738.2 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 5.56

Publications

0 publications found

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 Gene-Disease associations (from GenCC):

susceptibility to localized juvenile periodontitis
Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
Tourette syndrome
Inheritance: Unknown Classification: NO_KNOWN Submitted by: Labcorp Genetics (formerly Invitae)

FPR1 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_pathogenic. The variant received 6 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

PP3

MetaRNN computational evidence supports a deleterious effect, 0.986

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001005738.2. 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
	FPR2	NM_001005738.2	MANE Select	c.638C>A	p.Pro213Gln	missense	Exon 2 of 2	NP_001005738.1	P25090
	FPR2	NM_001462.3		c.638C>A	p.Pro213Gln	missense	Exon 2 of 2	NP_001453.1	P25090

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FPR2	ENST00000340023.7	TSL:1 MANE Select	c.638C>A	p.Pro213Gln	missense	Exon 2 of 2	ENSP00000340191.4	P25090
FPR2	ENST00000598776.1	TSL:1	c.638C>A	p.Pro213Gln	missense	Exon 2 of 2	ENSP00000468897.1	P25090
FPR2	ENST00000598953.1	TSL:2	c.638C>A	p.Pro213Gln	missense	Exon 3 of 3	ENSP00000468876.1	P25090

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

0.00000137

AC:

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

33480

American (AMR)

AF:

0.00

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.0000383

AC:

AN:

26136

East Asian (EAS)

AF:

0.00

AC:

AN:

39700

South Asian (SAS)

AF:

0.00

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.00

AC:

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

8.99e-7

AC:

AN:

1112012

Other (OTH)

AF:

0.00

AC:

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.550

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.95

BayesDel_addAF

Uncertain

0.051

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Uncertain

0.99

DEOGEN2

Uncertain

0.56

Eigen

Uncertain

0.56

Eigen_PC

Uncertain

0.29

FATHMM_MKL

Pathogenic

0.98

LIST_S2

Uncertain

0.90

M_CAP

Benign

0.012

MetaRNN

Pathogenic

0.99

MetaSVM

Uncertain

0.35

MutationAssessor

Pathogenic

4.9

PhyloP100

5.6

PrimateAI

Benign

0.39

PROVEAN

Pathogenic

-7.7

REVEL

Uncertain

0.43

Sift

Pathogenic

0.0

Sift4G

Pathogenic

0.0

Polyphen

1.0

Vest4

0.78

MutPred

0.87

Gain of catalytic residue at P213 (P = 0.0383)

MVP

0.67

MPC

0.98

ClinPred

1.0

GERP RS

3.8

Varity_R

0.85

gMVP

0.65

Mutation Taster

=56/44

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over