rs771397224

Variant names:

• chr5-76618207-C-T
• rs771397224
• NM_004101.4:c.500G>A

Variant summary

Our verdict is Likely benign. The variant received -1 ACMG points: 0P and 1B. BP4

The NM_004101.4(F2RL2):​c.500G>A​(p.Arg167Gln) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000669 in 1,613,982 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

• Frequency:
  • Genomes: 𝑓 0.00011 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000063 (0 hom.)
• Consequence: F2RL2 NM_004101.4 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.55
• Publications: 0 publications found

Genes affected

F2RL2 (HGNC:3539): (coagulation factor II thrombin receptor like 2) This gene encodes a member of the protease-activated receptor (PAR) family which is a subfamily of the seven transmembrane G protein-coupled cell surface receptor family. The encoded protein acts as a cofactor in the thrombin-mediated cleavage and activation of the protease-activated receptor family member PAR4. The encoded protein plays an essential role in hemostasis and thrombosis. Alternate splicing results in multiple transcript variants that encode different isoforms. [provided by RefSeq, Feb 2012]

IQGAP2 (HGNC:6111): (IQ motif containing GTPase activating protein 2) This gene encodes a member of the IQGAP family. The encoded protein contains three IQ domains, one calponin homology domain, one Ras-GAP domain and one WW domain. This protein interacts with components of the cytoskeleton, with cell adhesion molecules, and with several signaling molecules to regulate cell morphology and motility. It also acts as a tumor suppressor and has been found to play a role in regulating innate antiviral responses. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Apr 2017]

ACMG classification

Our verdict: Likely_benign. The variant received -1 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.3299933).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004101.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F2RL2	NM_004101.4	MANE Select	c.500G>A	p.Arg167Gln	missense	Exon 2 of 2	NP_004092.1	O00254-1
	IQGAP2	NM_006633.5	MANE Select	c.1521+7024C>T		intron	N/A	NP_006624.3	Q13576-1
	F2RL2	NM_001256566.2		c.434G>A	p.Arg145Gln	missense	Exon 2 of 2	NP_001243495.1	O00254-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F2RL2	ENST00000296641.5	TSL:1 MANE Select	c.500G>A	p.Arg167Gln	missense	Exon 2 of 2	ENSP00000296641.3	O00254-1
	IQGAP2	ENST00000274364.11	TSL:1 MANE Select	c.1521+7024C>T		intron	N/A	ENSP00000274364.6	Q13576-1
	IQGAP2	ENST00000396234.7	TSL:1	c.180+7024C>T		intron	N/A	ENSP00000379535.3	Q13576-2

Frequencies

GnomAD3 genomes AF: 0.000105 AC: 16 AN: 152108 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.000241

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: 0.0000882

Gnomad OTH AF: 0.00

GnomAD2 exomes AF: 0.0000876 AC: 22 AN: 251024 AF XY: 0.000118

Gnomad AFR exome AF: 0.000247

Gnomad AMR exome AF: 0.000116

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad FIN exome AF: 0.0000924

Gnomad NFE exome AF: 0.0000881

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000629 AC: 92 AN: 1461874 Hom.: 0 Cov.: 33 AF XY: 0.0000701 AC XY: 51 AN XY: 727234

African (AFR) AF: 0.000209 AC: 7 AN: 33480

American (AMR) AF: 0.0000671 AC: 3 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.0000348 AC: 3 AN: 86258

European-Finnish (FIN) AF: 0.0000749 AC: 4 AN: 53406

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5768

European-Non Finnish (NFE) AF: 0.0000647 AC: 72 AN: 1112006

Other (OTH) AF: 0.0000331 AC: 2 AN: 60396

GnomAD4 genome AF: 0.000105 AC: 16 AN: 152108 Hom.: 0 Cov.: 32 AF XY: 0.0000673 AC XY: 5 AN XY: 74294

African (AFR) AF: 0.000241 AC: 10 AN: 41410

American (AMR) AF: 0.00 AC: 0 AN: 15278

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5188

South Asian (SAS) AF: 0.00 AC: 0 AN: 4822

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10596

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.0000882 AC: 6 AN: 68022

Other (OTH) AF: 0.00 AC: 0 AN: 2092

Alfa AF: 0.0000772 Hom.: 0

Bravo AF: 0.000106

ExAC AF: 0.0000824 AC: 10

ClinVar

ClinVar submissions

Significance: Uncertain significance

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	1	-	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.25	T
BayesDel_noAF	Benign	-0.30
CADD	Benign	22
DANN	Pathogenic	1.0
DEOGEN2	Uncertain	0.50	T
Eigen	Uncertain	0.41
Eigen_PC	Uncertain	0.33
FATHMM_MKL	Uncertain	0.88	D
LIST_S2	Benign	0.74	T
M_CAP	Benign	0.062	D
MetaRNN	Benign	0.33	T
MetaSVM	Uncertain	-0.080	T
MutationAssessor	Uncertain	2.2	M
PhyloP100		1.6
PrimateAI	Benign	0.27	T
PROVEAN	Uncertain	-2.4	N
REVEL	Uncertain	0.50
Sift	Uncertain	0.013	D
Sift4G	Uncertain	0.015	D
Polyphen		1.0	D
Vest4		0.15
MVP		0.84
MPC		0.10
ClinPred		0.084	T
GERP RS		3.6
Varity_R		0.32
gMVP		0.54
Mutation Taster		=61/39	polymorphism

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

Other links and lift over

dbSNP: rs771397224; hg19: chr5-75914032; COSMIC: COSV105858302;