19-51768878-T-C

Variant names:

Variant summary

Our verdict is Benign. The variant received -16 ACMG points: 0P and 16B. BP4_StrongBP6_Very_StrongBS2

The NM_001005738.2(FPR2):c.220T>C(p.Phe74Leu) variant causes a missense change involving the alteration of a conserved nucleotide. The variant allele was found at a frequency of 0.0059 in 1,614,192 control chromosomes in the GnomAD database, including 35 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0044 ( 2 hom., cov: 32)

Exomes 𝑓: 0.0061 ( 33 hom. )

Consequence

FPR2
NM_001005738.2 missense

Scores

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 7.36

Publications

8 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: Benign. The variant received -16 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.009210765).

BP6

Variant 19-51768878-T-C is Benign according to our data. Variant chr19-51768878-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 781747.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS2

High Homozygotes in GnomAd4 at 2 gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FPR2	NM_001005738.2 link	c.220T>C	p.Phe74Leu	missense_variant	Exon 2 of 2	ENST00000340023.7	NP_001005738.1	P25090A0A024R4P3
FPR2	NM_001462.3 link	c.220T>C	p.Phe74Leu	missense_variant	Exon 2 of 2		NP_001453.1	P25090A0A024R4P3
FPR2	XM_006723120.4 link	c.220T>C	p.Phe74Leu	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.220T>C	p.Phe74Leu	missense_variant	Exon 2 of 2	1	NM_001005738.2	ENSP00000340191.4		P25090

Frequencies

GnomAD3 genomes

AF:

0.00438

AC:

666

AN:

152180

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000893

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00183

Gnomad ASJ

AF:

0.00432

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.0170

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00590

Gnomad OTH

AF:

0.00191

GnomAD2 exomes

AF:

0.00468

AC:

1177

AN:

251488

AF XY:

0.00451

show subpopulations

Gnomad AFR exome

AF:

0.000923

Gnomad AMR exome

AF:

0.00119

Gnomad ASJ exome

AF:

0.00208

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.0149

Gnomad NFE exome

AF:

0.00662

Gnomad OTH exome

AF:

0.00407

GnomAD4 exome

AF:

0.00606

AC:

8860

AN:

1461894

Hom.:

Cov.:

AF XY:

0.00576

AC XY:

4190

AN XY:

727248

show subpopulations

African (AFR)

AF:

0.000627

AC:

AN:

33480

American (AMR)

AF:

0.00127

AC:

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.00153

AC:

AN:

26136

East Asian (EAS)

AF:

0.0000252

AC:

AN:

39700

South Asian (SAS)

AF:

0.0000812

AC:

AN:

86258

European-Finnish (FIN)

AF:

0.0143

AC:

765

AN:

53420

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5768

European-Non Finnish (NFE)

AF:

0.00688

AC:

7652

AN:

1112012

Other (OTH)

AF:

0.00525

AC:

317

AN:

60396

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

Heterozygous variant carriers

625

1251

1876

2502

3127

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

AF:

0.00437

AC:

666

AN:

152298

Hom.:

Cov.:

AF XY:

0.00463

AC XY:

345

AN XY:

74482

show subpopulations

African (AFR)

AF:

0.000890

AC:

AN:

41574

American (AMR)

AF:

0.00183

AC:

AN:

15300

Ashkenazi Jewish (ASJ)

AF:

0.00432

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5176

South Asian (SAS)

AF:

0.00

AC:

AN:

4826

European-Finnish (FIN)

AF:

0.0170

AC:

181

AN:

10616

Middle Eastern (MID)

AF:

0.00

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.00590

AC:

401

AN:

68014

Other (OTH)

AF:

0.00189

AC:

AN:

2114

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.501

Heterozygous variant carriers

100

134

167

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00518

Hom.:

Bravo

AF:

0.00330

TwinsUK

AF:

0.00917

AC:

ALSPAC

AF:

0.00701

AC:

ESP6500AA

AF:

0.000681

AC:

ESP6500EA

AF:

0.00616

AC:

ExAC

AF:

0.00474

AC:

576

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00540

EpiControl

AF:

0.00528

ClinVar

Significance: Benign/Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

- -

Dec 31, 2019

Labcorp Genetics (formerly Invitae), Labcorp

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Sep 01, 2024

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FPR2: BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.97

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.22

CADD

Benign

(source)

DANN

Uncertain

1.0

DEOGEN2

Benign

0.36

.;T;.;T;T;.

Eigen

Uncertain

0.26

Eigen_PC

Benign

0.11

FATHMM_MKL

Uncertain

0.96

LIST_S2

Uncertain

0.93

D;.;T;.;T;D

MetaRNN

Benign

0.0092

T;T;T;T;T;T

MetaSVM

Uncertain

-0.27

MutationAssessor

Uncertain

2.4

.;M;.;M;M;.

PhyloP100

7.4

PrimateAI

Uncertain

0.62

PROVEAN

Pathogenic

-5.9

.;D;.;.;.;.

REVEL

Uncertain

0.46

Sift

Uncertain

0.0030

.;D;.;.;.;.

Sift4G

Benign

0.095

T;D;T;D;D;T

Polyphen

0.90

.;P;.;P;P;.

Vest4

0.39, 0.40

MutPred

0.72

Loss of catalytic residue at F74 (P = 0.0415);Loss of catalytic residue at F74 (P = 0.0415);Loss of catalytic residue at F74 (P = 0.0415);Loss of catalytic residue at F74 (P = 0.0415);Loss of catalytic residue at F74 (P = 0.0415);Loss of catalytic residue at F74 (P = 0.0415);

MVP

0.81

MPC

1.1

ClinPred

0.070

GERP RS

3.6

Varity_R

0.87

gMVP

0.38

Mutation Taster

=92/8

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

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19-51768878-T-C

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over