11-46719682-A-AC

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The NM_000506.5(F2):c.80-13dup variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000343 in 1,575,868 control chromosomes in the GnomAD database, with no homozygous occurrence. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.000033 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000034 (0 hom.)
• Consequence: F2 NM_000506.5 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 1.62

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 Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 11-46719682-A-AC is Benign according to our data. Variant chr11-46719682-A-AC is described in ClinVar as [Benign]. Clinvar id is 2870553.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
F2	NM_000506.5	c.80-13dup		intron_variant		ENST00000311907.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
F2	ENST00000311907.10	c.80-13dup		intron_variant		1	NM_000506.5	P1
F2	ENST00000442468.1	c.50-13dup		intron_variant		3
F2	ENST00000530231.5	c.80-13dup		intron_variant		5
F2	ENST00000469189.1	n.120-13dup		intron_variant, non_coding_transcript_variant		2

Frequencies

GnomAD3 genomes AF: 0.0000332 AC: 5 AN: 150706 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000244

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000195

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.0000962

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000148

Gnomad OTH AF: 0.000484

GnomAD3 exomes AF: 0.000103 AC: 20 AN: 194730 Hom.: 0 AF XY: 0.0000672 AC XY: 7 AN XY: 104196

Gnomad AFR exome AF: 0.0000834

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000804

Gnomad SAS exome AF: 0.0000405

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000725

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000344 AC: 49 AN: 1425048 Hom.: 0 Cov.: 31 AF XY: 0.0000354 AC XY: 25 AN XY: 705368

Gnomad4 AFR exome AF: 0.0000306

Gnomad4 AMR exome AF: 0.0000250

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.000290

Gnomad4 SAS exome AF: 0.0000743

Gnomad4 FIN exome AF: 0.0000594

Gnomad4 NFE exome AF: 0.0000201

Gnomad4 OTH exome AF: 0.0000678

GnomAD4 genome AF: 0.0000332 AC: 5 AN: 150820 Hom.: 0 Cov.: 32 AF XY: 0.0000543 AC XY: 4 AN XY: 73598

Gnomad4 AFR AF: 0.0000244

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000195

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.0000962

Gnomad4 NFE AF: 0.0000148

Gnomad4 OTH AF: 0.000479

Bravo AF: 0.0000378

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

Congenital prothrombin deficiency Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Aug 16, 2023

- -

Computational scores

Source: dbNSFP v4.3

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: rs745681370; hg19: chr11-46741232;