chr5-76733376-G-C

Position:

• chr5-76733376-G-C

Variant summary

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

The NM_001992.5(F2R):​c.1151G>C​(p.Ser384Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000684 in 1,461,892 control chromosomes in the GnomAD database, with no homozygous occurrence. 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 (★).

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: F2R NM_001992.5 missense
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 1.32

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=0.119589925).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F2R	NM_001992.5	c.1151G>C	p.Ser384Thr	missense_variant	2/2	ENST00000319211.5
F2R	NM_001311313.2	c.788G>C	p.Ser263Thr	missense_variant	3/3

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F2R	ENST00000319211.5	c.1151G>C	p.Ser384Thr	missense_variant	2/2	1	NM_001992.5	P1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461892 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727248

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000224

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: 0.00

Gnomad4 OTH exome AF: 0.00

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

Jan 02, 2024

The c.1151G>C (p.S384T) alteration is located in exon 2 (coding exon 2) of the F2R gene. This alteration results from a G to C substitution at nucleotide position 1151, causing the serine (S) at amino acid position 384 to be replaced by a threonine (T). 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	0.089
BayesDel_addAF	Benign	-0.26	T
BayesDel_noAF	Benign	-0.61
CADD	Benign	15
DANN	Benign	0.95
DEOGEN2	Uncertain	0.50	T
Eigen	Benign	-0.67
Eigen_PC	Benign	-0.75
FATHMM_MKL	Benign	0.36	N
LIST_S2	Benign	0.54	T
M_CAP	Benign	0.0080	T
MetaRNN	Benign	0.12	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.9	L
MutationTaster	Benign	1.0	N
PrimateAI	Benign	0.32	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.025
Sift	Uncertain	0.020	D
Sift4G	Benign	0.23	T
Polyphen		0.36	B
Vest4		0.18
MutPred		0.35		Loss of disorder (P = 0.0512);
MVP		0.48
MPC		0.31
ClinPred		0.12	T
GERP RS		0.90
Varity_R		0.093
gMVP		0.091

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

LitVar

Other links and lift over

dbSNP: rs1748718333; hg19: chr5-76029201;