Variant 5-76716369-C-A details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_001311313.2(F2R):c.-424C>A variant causes a 5 prime UTR premature start codon gain 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. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)

Exomes 𝑓: 7.6e-7 ( 0 hom. )

Consequence

F2R
NM_001311313.2 5_prime_UTR_premature_start_codon_gain

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 0.814

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:

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ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

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

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
F2R	NM_001992.5 link	c.62C>A	p.Ser21Tyr	missense_variant	1/2	ENST00000319211.5	NP_001983.2	P25116A0A024RAP7
F2R	NM_001311313.2 link	c.-424C>A		5_prime_UTR_premature_start_codon_gain_variant	1/3		NP_001298242.1	P25116
F2R	NM_001311313.2 link	c.-424C>A		5_prime_UTR_variant	1/3		NP_001298242.1	P25116

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
F2R	ENST00000319211.5 link	c.62C>A	p.Ser21Tyr	missense_variant	1/2	1	NM_001992.5	ENSP00000321326.4		P25116
F2R	ENST00000505600.1 link	c.62C>A	p.Ser21Tyr	missense_variant	1/2	2		ENSP00000426398.1		G3XAL6

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

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:

9.59e-7

Gnomad4 OTH exome

AF:

0.00

GnomAD4 genome

Cov.:

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Nov 06, 2024

The c.62C>A (p.S21Y) alteration is located in exon 1 (coding exon 1) of the F2R gene. This alteration results from a C to A substitution at nucleotide position 62, causing the serine (S) at amino acid position 21 to be replaced by a tyrosine (Y). 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

0.13

BayesDel_addAF

Benign

-0.10

BayesDel_noAF

Benign

-0.39

CADD

Benign

DANN

Benign

0.93

DEOGEN2

Uncertain

0.50

T;.

Eigen

Benign

-0.93

Eigen_PC

Benign

-1.1

FATHMM_MKL

Benign

0.11

LIST_S2

Benign

0.69

T;T

M_CAP

Uncertain

0.25

MetaRNN

Benign

0.16

T;T

MetaSVM

Benign

-0.78

MutationAssessor

Benign

1.9

L;.

PrimateAI

Pathogenic

0.80

PROVEAN

Benign

-0.48

N;D

REVEL

Benign

0.17

Sift

Benign

0.45

T;.

Sift4G

Benign

0.55

T;D

Polyphen

0.063

B;.

Vest4

0.20

MutPred

0.36

Loss of disorder (P = 7e-04);Loss of disorder (P = 7e-04);

MVP

0.75

MPC

2.3

ClinPred

0.11

GERP RS

-2.1

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.073

gMVP

0.54

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

No publications associated with this variant yet.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over