19-51768827-C-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001005738.2(FPR2):​c.169C>T​(p.Arg57Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000114 in 1,614,120 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 12/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000099 ( 0 hom., cov: 32)
Exomes 𝑓: 0.00012 ( 0 hom. )

Consequence

FPR2
NM_001005738.2 missense

Scores

1
4
14

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.16
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]
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (MetaRNN=0.19074282).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FPR2NM_001005738.2 linkc.169C>T p.Arg57Cys missense_variant Exon 2 of 2 ENST00000340023.7 NP_001005738.1 P25090A0A024R4P3
FPR2NM_001462.3 linkc.169C>T p.Arg57Cys missense_variant Exon 2 of 2 NP_001453.1 P25090A0A024R4P3
FPR2XM_006723120.4 linkc.169C>T p.Arg57Cys missense_variant Exon 3 of 3 XP_006723183.1 P25090A0A024R4P3

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FPR2ENST00000340023.7 linkc.169C>T p.Arg57Cys missense_variant Exon 2 of 2 1 NM_001005738.2 ENSP00000340191.4 P25090

Frequencies

GnomAD3 genomes
AF:
0.0000986
AC:
15
AN:
152108
Hom.:
0
Cov.:
32
show subpopulations
Gnomad AFR
AF:
0.000217
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.000193
Gnomad SAS
AF:
0.000208
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.0000588
Gnomad OTH
AF:
0.00
GnomAD3 exomes
AF:
0.0000954
AC:
24
AN:
251478
Hom.:
0
AF XY:
0.0000957
AC XY:
13
AN XY:
135908
show subpopulations
Gnomad AFR exome
AF:
0.000369
Gnomad AMR exome
AF:
0.00
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.000217
Gnomad SAS exome
AF:
0.0000980
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.0000967
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.000116
AC:
169
AN:
1461894
Hom.:
0
Cov.:
31
AF XY:
0.000121
AC XY:
88
AN XY:
727248
show subpopulations
Gnomad4 AFR exome
AF:
0.000239
Gnomad4 AMR exome
AF:
0.0000224
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000151
Gnomad4 SAS exome
AF:
0.000162
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.000120
Gnomad4 OTH exome
AF:
0.000116
GnomAD4 genome
AF:
0.0000985
AC:
15
AN:
152226
Hom.:
0
Cov.:
32
AF XY:
0.000107
AC XY:
8
AN XY:
74420
show subpopulations
Gnomad4 AFR
AF:
0.000217
Gnomad4 AMR
AF:
0.00
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.000193
Gnomad4 SAS
AF:
0.000208
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.0000588
Gnomad4 OTH
AF:
0.00
Alfa
AF:
0.000172
Hom.:
0
Bravo
AF:
0.000128
TwinsUK
AF:
0.00
AC:
0
ALSPAC
AF:
0.000519
AC:
2
ESP6500AA
AF:
0.000454
AC:
2
ESP6500EA
AF:
0.000349
AC:
3
ExAC
AF:
0.000132
AC:
16
EpiCase
AF:
0.0000545
EpiControl
AF:
0.000296

ClinVar

Significance: Uncertain significance
Submissions summary: Uncertain:1
Revision: criteria provided, single submitter
LINK: link

Submissions by phenotype

not specified Uncertain:1
Dec 22, 2023
Ambry Genetics
Significance: Uncertain significance
Review Status: criteria provided, single submitter
Collection Method: clinical testing

The c.169C>T (p.R57C) 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 169, causing the arginine (R) at amino acid position 57 to be replaced by a cysteine (C). 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
Benign
0.22
BayesDel_addAF
Benign
-0.28
T
BayesDel_noAF
Benign
-0.34
CADD
Benign
21
DANN
Uncertain
1.0
DEOGEN2
Uncertain
0.52
.;D;.;D;D;.
Eigen
Benign
0.068
Eigen_PC
Benign
0.11
FATHMM_MKL
Benign
0.76
D
LIST_S2
Benign
0.30
T;.;T;.;T;T
M_CAP
Benign
0.0069
T
MetaRNN
Benign
0.19
T;T;T;T;T;T
MetaSVM
Benign
-0.68
T
MutationAssessor
Uncertain
2.4
.;M;.;M;M;.
PrimateAI
Benign
0.29
T
PROVEAN
Pathogenic
-4.6
.;D;.;.;.;.
REVEL
Benign
0.18
Sift
Uncertain
0.0010
.;D;.;.;.;.
Sift4G
Benign
0.074
T;T;D;T;T;D
Polyphen
0.15
.;B;.;B;B;.
Vest4
0.15, 0.15
MVP
0.57
MPC
0.51
ClinPred
0.20
T
GERP RS
3.6
Varity_R
0.30
gMVP
0.49

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.

Other links and lift over

dbSNP: rs142611552; hg19: chr19-52272080; COSMIC: COSV60673468; API