19-51768827-C-T

Variant names:

• chr19-51768827-C-T
• rs142611552
• NM_001005738.2:c.169C>T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 3.16

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]

ACMG classification

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
FPR2	NM_001005738.2	c.169C>T	p.Arg57Cys	missense_variant	Exon 2 of 2	ENST00000340023.7	NP_001005738.1
FPR2	NM_001462.3	c.169C>T	p.Arg57Cys	missense_variant	Exon 2 of 2		NP_001453.1
FPR2	XM_006723120.4	c.169C>T	p.Arg57Cys	missense_variant	Exon 3 of 3		XP_006723183.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FPR2	ENST00000340023.7	c.169C>T	p.Arg57Cys	missense_variant	Exon 2 of 2	1	NM_001005738.2	ENSP00000340191.4

Frequencies

GnomAD3 genomes AF: 0.0000986 AC: 15 AN: 152108 Hom.: 0 Cov.: 32

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

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

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

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

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

Other links and lift over

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