5-76716369-C-A

Variant names:

• chr5-76716369-C-A
• NM_001992.5:c.62C>A

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_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. 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_001311313.2 5_prime_UTR_premature_start_codon_gain
• Clinical Significance: Uncertain significance criteria provided, single submitter U:1
• Conservation: PhyloP100: 0.814

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]

ENSG00000225407 (HGNC:):

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=0.15949437).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
F2R	NM_001992.5	c.62C>A	p.Ser21Tyr	missense_variant	Exon 1 of 2	ENST00000319211.5	NP_001983.2
F2R	NM_001311313.2	c.-424C>A		5_prime_UTR_premature_start_codon_gain_variant	Exon 1 of 3		NP_001298242.1
F2R	NM_001311313.2	c.-424C>A		5_prime_UTR_variant	Exon 1 of 3		NP_001298242.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
F2R	ENST00000319211.5	c.62C>A	p.Ser21Tyr	missense_variant	Exon 1 of 2	1	NM_001992.5	ENSP00000321326.4
F2R	ENST00000505600.1	c.62C>A	p.Ser21Tyr	missense_variant	Exon 1 of 2	2		ENSP00000426398.1
ENSG00000225407	ENST00000507514.1	n.-154G>T		upstream_gene_variant		3

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 7.64e-7 AC: 1 AN: 1308926 Hom.: 0 Cov.: 31 AF XY: 0.00000156 AC XY: 1 AN XY: 640568

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.: 33

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

Submissions by phenotype

not specified Uncertain:1

Nov 06, 2024

Ambry Genetics

Significance: Uncertain significance

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	13
DANN	Benign	0.93
DEOGEN2	Uncertain	0.50	T;.
Eigen	Benign	-0.93
Eigen_PC	Benign	-1.1
FATHMM_MKL	Benign	0.11	N
LIST_S2	Benign	0.69	T;T
M_CAP	Uncertain	0.25	D
MetaRNN	Benign	0.16	T;T
MetaSVM	Benign	-0.78	T
MutationAssessor	Benign	1.9	L;.
PrimateAI	Pathogenic	0.80	T
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	T
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.

Other links and lift over

hg19: chr5-76012194;