11-46719682-AC-A

Variant names:

• chr11-46719682-AC-A
• rs745681370
• NM_000506.5:c.80-13delC

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000506.5(F2):​c.80-13delC variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000161 in 1,425,070 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: not found (cov: 32)
  • Exomes 𝑓: 0.000016 (0 hom.)
• Consequence: F2 NM_000506.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62
• Publications: 0 publications found

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]

F2 Gene-Disease associations (from GenCC):

• thrombophilia due to thrombin defect

  Inheritance: AD Classification: DEFINITIVE, STRONG Submitted by: Genomics England PanelApp, ClinGen, Labcorp Genetics (formerly Invitae)
• congenital prothrombin deficiency

  Inheritance: AR Classification: DEFINITIVE, STRONG, SUPPORTIVE Submitted by: ClinGen, Laboratory for Molecular Medicine, Labcorp Genetics (formerly Invitae), Orphanet

ACMG classification

Our verdict: Likely_benign. The variant received -2 ACMG points.

• BP6: Variant 11-46719682-AC-A is Benign according to our data. Variant chr11-46719682-AC-A is described in ClinVar as Benign. ClinVar VariationId is 3674541.Status of the report is criteria_provided_single_submitter, 1 stars.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000506.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F2	NM_000506.5	MANE Select	c.80-13delC		intron	N/A	NP_000497.1	P00734

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	F2	ENST00000311907.10	TSL:1 MANE Select	c.80-19delC		intron	N/A	ENSP00000308541.5	P00734
	F2	ENST00000862106.1		c.80-19delC		intron	N/A	ENSP00000532165.1
	F2	ENST00000862118.1		c.80-19delC		intron	N/A	ENSP00000532177.1

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD2 exomes AF: 0.0000462 AC: 9 AN: 194730 AF XY: 0.0000480

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000344

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0000575

Gnomad NFE exome AF: 0.0000845

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000161 AC: 23 AN: 1425070 Hom.: 0 Cov.: 31 AF XY: 0.0000170 AC XY: 12 AN XY: 705376

African (AFR) AF: 0.00 AC: 0 AN: 32652

American (AMR) AF: 0.0000501 AC: 2 AN: 39922

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25364

East Asian (EAS) AF: 0.00 AC: 0 AN: 37940

South Asian (SAS) AF: 0.00 AC: 0 AN: 80806

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 50556

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4254

European-Non Finnish (NFE) AF: 0.0000174 AC: 19 AN: 1094570

Other (OTH) AF: 0.0000339 AC: 2 AN: 59006

GnomAD4 genome Cov.: 32

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.00000378

ClinVar

ClinVar submissions

Significance: Benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	Congenital prothrombin deficiency (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		1.6
BranchPoint Hunter		4.0

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.030		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs745681370; hg19: chr11-46741232;