19-51769394-G-A

Variant names:

• chr19-51769394-G-A
• rs1361960096
• NM_001005738.2:c.736G>A

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_001005738.2(FPR2):​c.736G>A​(p.Val246Met) variant causes a missense change. The variant allele was found at a frequency of 0.00000958 in 1,461,888 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.0000096 (0 hom.)
• Consequence: FPR2 NM_001005738.2 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 4.83

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 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FPR2	NM_001005738.2	c.736G>A	p.Val246Met	missense_variant	Exon 2 of 2	ENST00000340023.7	NP_001005738.1
FPR2	NM_001462.3	c.736G>A	p.Val246Met	missense_variant	Exon 2 of 2		NP_001453.1
FPR2	XM_006723120.4	c.736G>A	p.Val246Met	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.736G>A	p.Val246Met	missense_variant	Exon 2 of 2	1	NM_001005738.2	ENSP00000340191.4
FPR2	ENST00000598776.1	c.736G>A	p.Val246Met	missense_variant	Exon 2 of 2	1		ENSP00000468897.1
FPR2	ENST00000598953.1	c.736G>A	p.Val246Met	missense_variant	Exon 3 of 3	2		ENSP00000468876.1
FPR1	ENST00000594900.2	c.-12+8251C>T		intron_variant	Intron 2 of 2	4		ENSP00000470750.2

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD3 exomes AF: 0.00000398 AC: 1 AN: 251460 Hom.: 0 AF XY: 0.00 AC XY: 0 AN XY: 135910

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: 0.00000879

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000958 AC: 14 AN: 1461888 Hom.: 0 Cov.: 31 AF XY: 0.00000825 AC XY: 6 AN XY: 727244

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: 0.0000117

Gnomad4 OTH exome AF: 0.0000166

GnomAD4 genome Cov.: 32

EpiCase AF: 0.0000545

EpiControl AF: 0.00

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Oct 12, 2022

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The c.736G>A (p.V246M) alteration is located in exon 2 (coding exon 1) of the FPR2 gene. This alteration results from a G to A substitution at nucleotide position 736, causing the valine (V) at amino acid position 246 to be replaced by a methionine (M). 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	Uncertain	0.52
BayesDel_addAF	Benign	-0.020	T
BayesDel_noAF	Benign	-0.27
CADD	Uncertain	25
DANN	Uncertain	1.0
DEOGEN2	Benign	0.33	T;T;T
Eigen	Uncertain	0.56
Eigen_PC	Uncertain	0.39
FATHMM_MKL	Uncertain	0.94	D
LIST_S2	Uncertain	0.94	.;.;D
M_CAP	Benign	0.0072	T
MetaRNN	Uncertain	0.53	D;D;D
MetaSVM	Uncertain	-0.16	T
MutationAssessor	Pathogenic	3.4	M;M;M
PrimateAI	Benign	0.44	T
PROVEAN	Uncertain	-2.9	D;.;.
REVEL	Uncertain	0.34
Sift	Uncertain	0.0010	D;.;.
Sift4G	Uncertain	0.0020	D;D;D
Polyphen		1.0	D;D;D
Vest4		0.43
MutPred		0.68		Gain of catalytic residue at V242 (P = 0.0219);Gain of catalytic residue at V242 (P = 0.0219);Gain of catalytic residue at V242 (P = 0.0219);
MVP		0.76
MPC		1.0
ClinPred		0.99	D
GERP RS		3.8
Varity_R		0.60
gMVP		0.40

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: rs1361960096; hg19: chr19-52272647;