5-76733027-G-T

Position:

• chr5-76733027-G-T

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_001992.5(F2R):​c.802G>T​(p.Ala268Ser) 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. 15/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. A268P) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 32)
• Consequence: F2R NM_001992.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: -0.0630

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]

ACMG classification

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=0.076619595).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F2R	NM_001992.5	c.802G>T	p.Ala268Ser	missense_variant	2/2	ENST00000319211.5
F2R	NM_001311313.2	c.439G>T	p.Ala147Ser	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F2R	ENST00000319211.5	c.802G>T	p.Ala268Ser	missense_variant	2/2	1	NM_001992.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome Cov.: 31

GnomAD4 genome Cov.: 32

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Uncertain significance, criteria provided, single submitter

clinical testing

Ambry Genetics

Jul 25, 2023

The c.802G>T (p.A268S) alteration is located in exon 2 (coding exon 2) of the F2R gene. This alteration results from a G to T substitution at nucleotide position 802, causing the alanine (A) at amino acid position 268 to be replaced by a serine (S). 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	0.087
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	10
DANN	Benign	0.91
DEOGEN2	Benign	0.38	T
Eigen	Benign	-0.94
Eigen_PC	Benign	-0.88
FATHMM_MKL	Benign	0.29	N
LIST_S2	Benign	0.56	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.077	T
MetaSVM	Benign	-1.0	T
MutationAssessor	Benign	0.35	N
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.29	T
PROVEAN	Benign	0.13	N
REVEL	Benign	0.0080
Sift	Benign	0.11	T
Sift4G	Benign	0.78	T
Polyphen		0.0070	B
Vest4		0.053
MutPred		0.43		Loss of helix (P = 0.2022);
MVP		0.39
MPC		0.30
ClinPred		0.033	T
GERP RS		1.7
Varity_R		0.039
gMVP		0.26

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.

Other links and lift over

hg19: chr5-76028852;