Genetic Variant NM_004101.4:c.503C>T (chr5-76618204-G-A) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004101.4(F2RL2):c.503C>T(p.Ala168Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. In-silico tool predicts a benign outcome for this variant. 16/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A168D) has been classified as Uncertain significance.

Frequency

Genomes: not found (cov: 32)

Consequence

F2RL2
NM_004101.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.513

Publications

1 publications found

Variant links:

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]

F2RL2 links:

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]

IQGAP2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.020484328).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
F2RL2	NM_004101.4	MANE Select	c.503C>T	p.Ala168Val	missense	Exon 2 of 2	NP_004092.1	O00254-1
IQGAP2	NM_006633.5	MANE Select	c.1521+7021G>A		intron	N/A	NP_006624.3	Q13576-1
F2RL2	NM_001256566.2		c.437C>T	p.Ala146Val	missense	Exon 2 of 2	NP_001243495.1	O00254-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
F2RL2	ENST00000296641.5	TSL:1 MANE Select	c.503C>T	p.Ala168Val	missense	Exon 2 of 2	ENSP00000296641.3	O00254-1
IQGAP2	ENST00000274364.11	TSL:1 MANE Select	c.1521+7021G>A		intron	N/A	ENSP00000274364.6	Q13576-1
IQGAP2	ENST00000396234.7	TSL:1	c.180+7021G>A		intron	N/A	ENSP00000379535.3	Q13576-2

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

Cov.:

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.070

BayesDel_addAF

Benign

-0.30

BayesDel_noAF

Benign

-0.66

CADD

Benign

2.4

(source)

DANN

Benign

0.67

DEOGEN2

Benign

0.092

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.034

LIST_S2

Benign

0.69

M_CAP

Benign

0.0040

MetaRNN

Benign

0.020

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.91

PhyloP100

0.51

PrimateAI

Benign

0.27

PROVEAN

Benign

2.4

REVEL

Benign

0.077

Sift

Benign

1.0

Sift4G

Benign

1.0

Polyphen

0.0030

Vest4

0.060

MutPred

0.39

Loss of methylation at R167 (P = 0.1086)

MVP

0.29

MPC

0.044

ClinPred

0.050

GERP RS

-5.6

Varity_R

0.060

gMVP

0.14

Mutation Taster

=96/4

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over