Genetic Variant NM_001992.5:c.62C>A (chr5-76716369-C-A) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001992.5(F2R):c.62C>A(p.Ser21Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000764 in 1,308,926 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

F2R
NM_001992.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.814

Publications

0 publications found

Variant links:

Genes affected

F2R (HGNC:3537): (coagulation factor II thrombin receptor) Coagulation factor II receptor is a 7-transmembrane receptor involved in the regulation of thrombotic response. Proteolytic cleavage leads to the activation of the receptor. F2R is a G-protein coupled receptor family member. Alternative splicing results in multiple transcript variants. [provided by RefSeq, Aug 2015]

F2R links:

ENSG00000225407 (HGNC:):

ENSG00000225407 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.15949437).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001992.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
F2R	NM_001992.5	MANE Select	c.62C>A	p.Ser21Tyr	missense	Exon 1 of 2	NP_001983.2	P25116
F2R	NM_001311313.2		c.-424C>A		5_prime_UTR_premature_start_codon_gain	Exon 1 of 3	NP_001298242.1
F2R	NM_001311313.2		c.-424C>A		5_prime_UTR	Exon 1 of 3	NP_001298242.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
F2R	ENST00000319211.5	TSL:1 MANE Select	c.62C>A	p.Ser21Tyr	missense	Exon 1 of 2	ENSP00000321326.4	P25116
F2R	ENST00000505600.1	TSL:2	c.62C>A	p.Ser21Tyr	missense	Exon 1 of 2	ENSP00000426398.1	G3XAL6
ENSG00000225407	ENST00000507514.1	TSL:3	n.-154G>T		upstream_gene	N/A

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.64e-7

AC:

AN:

1308926

Hom.:

Cov.:

AF XY:

0.00000156

AC XY:

AN XY:

640568

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

27396

American (AMR)

AF:

0.00

AC:

AN:

24278

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

22120

East Asian (EAS)

AF:

0.00

AC:

AN:

30866

South Asian (SAS)

AF:

0.00

AC:

AN:

68752

European-Finnish (FIN)

AF:

0.00

AC:

AN:

33152

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5420

European-Non Finnish (NFE)

AF:

9.59e-7

AC:

AN:

1042278

Other (OTH)

AF:

0.00

AC:

AN:

54664

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Cov.:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

(source)

DANN

Benign

0.93

DEOGEN2

Uncertain

0.50

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.69

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.16

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.9

PhyloP100

0.81

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.48

REVEL

Benign

0.17

Sift

Benign

0.45

Sift4G

Benign

0.55

Polyphen

0.063

Vest4

0.20

MutPred

0.36

Loss of disorder (P = 7e-04)

MVP

0.75

MPC

2.3

ClinPred

0.11

GERP RS

-2.1

PromoterAI

-0.077

Neutral

(source)

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.073

gMVP

0.54

Mutation Taster

=70/30

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over