rs2070851

chr11-46722978-T-C

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

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
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

ACMG classification

Verdict is Benign. Variant got -14 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_single_submitter, 1 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	UniProt
F2	NM_000506.5	c.317-202T>C		intron_variant		ENST00000311907.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F2	ENST00000311907.10	c.317-202T>C		intron_variant		1	NM_000506.5	P1
F2	ENST00000442468.1	c.287-202T>C		intron_variant		3
F2	ENST00000530231.5	c.317-202T>C		intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.212 AC: 32244 AN: 152052 Hom.: 4284 Cov.: 32

Gnomad AFR AF: 0.0826

Gnomad AMI AF: 0.255

Gnomad AMR AF: 0.286

Gnomad ASJ AF: 0.172

Gnomad EAS AF: 0.592

Gnomad SAS AF: 0.275

Gnomad FIN AF: 0.322

Gnomad MID AF: 0.209

Gnomad NFE AF: 0.226

Gnomad OTH AF: 0.198

GnomAD4 exome AF: 0.260 AC: 135018 AN: 518338 Hom.: 21093 AF XY: 0.260 AC XY: 72546 AN XY: 279306

Gnomad4 AFR exome AF: 0.0758

Gnomad4 AMR exome AF: 0.402

Gnomad4 ASJ exome AF: 0.169

Gnomad4 EAS exome AF: 0.609

Gnomad4 SAS exome AF: 0.275

Gnomad4 FIN exome AF: 0.297

Gnomad4 NFE exome AF: 0.220

Gnomad4 OTH exome AF: 0.229

GnomAD4 genome AF: 0.212 AC: 32253 AN: 152170 Hom.: 4292 Cov.: 32 AF XY: 0.221 AC XY: 16430 AN XY: 74380

Gnomad4 AFR AF: 0.0824

Gnomad4 AMR AF: 0.287

Gnomad4 ASJ AF: 0.172

Gnomad4 EAS AF: 0.593

Gnomad4 SAS AF: 0.275

Gnomad4 FIN AF: 0.322

Gnomad4 NFE AF: 0.226

Gnomad4 OTH AF: 0.193

Alfa AF: 0.211 Hom.: 573

Bravo AF: 0.207

Asia WGS AF: 0.338 AC: 1174 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Nov 10, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	6.3
Dann	Benign	0.76

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: rs2070851; hg19: chr11-46744528;