19-51769392-C-T

Variant names:

Variant summary

Our verdict is Uncertain significance. Variant got 1 ACMG points: 2P and 1B. PM2BP4

The NM_001005738.2(FPR2):c.734C>T(p.Ala245Val) variant causes a missense change. The variant allele was found at a frequency of 0.00000867 in 1,614,114 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 0.000020 ( 0 hom., cov: 32)

Exomes 𝑓: 0.0000075 ( 0 hom. )

Consequence

FPR2
NM_001005738.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 4.45

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.328389).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FPR2	NM_001005738.2 link	c.734C>T	p.Ala245Val	missense_variant	Exon 2 of 2	ENST00000340023.7	NP_001005738.1	P25090A0A024R4P3
FPR2	NM_001462.3 link	c.734C>T	p.Ala245Val	missense_variant	Exon 2 of 2		NP_001453.1	P25090A0A024R4P3
FPR2	XM_006723120.4 link	c.734C>T	p.Ala245Val	missense_variant	Exon 3 of 3		XP_006723183.1	P25090A0A024R4P3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	UniProt
FPR2	ENST00000340023.7 link	c.734C>T	p.Ala245Val	missense_variant	Exon 2 of 2	1	NM_001005738.2	ENSP00000340191.4	P25090
FPR2	ENST00000598776.1 link	c.734C>T	p.Ala245Val	missense_variant	Exon 2 of 2	1		ENSP00000468897.1	P25090
FPR2	ENST00000598953.1 link	c.734C>T	p.Ala245Val	missense_variant	Exon 3 of 3	2		ENSP00000468876.1	P25090
FPR1	ENST00000594900.2 link	c.-12+8253G>A		intron_variant	Intron 2 of 2	4		ENSP00000470750.2	P21462M0QZT0

Frequencies

GnomAD3 genomes

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.0000441

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000795

AC:

AN:

251452

Hom.:

AF XY:

0.0000147

AC XY:

AN XY:

135906

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000176

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.00000752

AC:

AN:

1461886

Hom.:

Cov.:

AF XY:

0.00000688

AC XY:

AN XY:

727240

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.00

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000989

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

AF:

0.0000197

AC:

AN:

152228

Hom.:

Cov.:

AF XY:

0.0000269

AC XY:

AN XY:

74362

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0000986

Hom.:

Bravo

AF:

0.0000151

ExAC

AF:

0.00000824

AC:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Jul 22, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.734C>T (p.A245V) 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 734, causing the alanine (A) at amino acid position 245 to be replaced by a valine (V). 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

0.19

BayesDel_addAF

Benign

-0.18

BayesDel_noAF

Benign

-0.48

CADD

Benign

DANN

Uncertain

1.0

DEOGEN2

Benign

0.16

T;T;T

Eigen

Benign

0.031

Eigen_PC

Benign

-0.057

FATHMM_MKL

Uncertain

0.89

LIST_S2

Uncertain

0.86

.;.;D

M_CAP

Benign

0.0058

MetaRNN

Benign

0.33

T;T;T

MetaSVM

Benign

-0.91

MutationAssessor

Benign

1.9

L;L;L

PrimateAI

Benign

0.44

PROVEAN

Uncertain

-3.2

D;.;.

REVEL

Benign

0.15

Sift

Benign

0.040

D;.;.

Sift4G

Uncertain

0.052

T;T;T

Polyphen

0.73

P;P;P

Vest4

0.32

MutPred

0.62

Gain of MoRF binding (P = 0.1389);Gain of MoRF binding (P = 0.1389);Gain of MoRF binding (P = 0.1389);

MVP

0.61

MPC

0.96

ClinPred

0.96

GERP RS

1.6

Varity_R

0.26

gMVP

0.17

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