rs2070851
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Variant summary
Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1
The NM_000506.5(F2):c.317-202T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.249 in 670,508 control chromosomes in the GnomAD database, including 25,385 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).
Frequency
Genomes: 𝑓 0.21 ( 4292 hom., cov: 32)
Exomes 𝑓: 0.26 ( 21093 hom. )
Consequence
F2
NM_000506.5 intron
NM_000506.5 intron
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.840
Genes affected
F2 (HGNC:3535): (coagulation factor II, thrombin) This gene encodes the prothrombin protein (also known as coagulation factor II). This protein is proteolytically cleaved in multiple steps to form the activated serine protease thrombin. The activated thrombin enzyme plays an important role in thrombosis and hemostasis by converting fibrinogen to fibrin during blood clot formation, by stimulating platelet aggregation, and by activating additional coagulation factors. Thrombin also plays a role in cell proliferation, tissue repair, and angiogenesis as well as maintaining vascular integrity during development and postnatal life. Peptides derived from the C-terminus of this protein have antimicrobial activity against E. coli and P. aeruginosa. Mutations in this gene lead to various forms of thrombosis and dysprothrombinemia. Rapid increases in cytokine levels following coronavirus infections can dysregulate the coagulation cascade and produce thrombosis, compromised blood supply, and organ failure. [provided by RefSeq, May 2020]
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ACMG classification
Classification made for transcript
Verdict is Benign. Variant got -20 ACMG points.
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.83).
BP6
Variant 11-46722978-T-C is Benign according to our data. Variant chr11-46722978-T-C is described in ClinVar as [Benign]. Clinvar id is 1183393.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BA1
GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.575 is higher than 0.05.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | Protein | UniProt |
---|---|---|---|---|---|---|---|---|
F2 | NM_000506.5 | c.317-202T>C | intron_variant | ENST00000311907.10 | NP_000497.1 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Protein | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|---|
F2 | ENST00000311907.10 | c.317-202T>C | intron_variant | 1 | NM_000506.5 | ENSP00000308541 | P1 | |||
F2 | ENST00000442468.1 | c.287-202T>C | intron_variant | 3 | ENSP00000387413 | |||||
F2 | ENST00000530231.5 | c.317-202T>C | intron_variant | 5 | ENSP00000433907 |
Frequencies
GnomAD3 genomes AF: 0.212 AC: 32244AN: 152052Hom.: 4284 Cov.: 32
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GnomAD4 exome AF: 0.260 AC: 135018AN: 518338Hom.: 21093 AF XY: 0.260 AC XY: 72546AN XY: 279306
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GnomAD4 genome AF: 0.212 AC: 32253AN: 152170Hom.: 4292 Cov.: 32 AF XY: 0.221 AC XY: 16430AN XY: 74380
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ClinVar
Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
Benign, criteria provided, single submitter | clinical testing | GeneDx | Nov 10, 2018 | - - |
Computational scores
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at