rs2070863

Variant names:

Your query was ambiguous. Multiple possible variants found:

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_000934.4(SERPINF2):c.97C>G(p.Arg33Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000707 in 1,413,466 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 15/22 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R33W) has been classified as Benign.

Frequency

Genomes: not found (cov: 26)

Exomes 𝑓: 7.1e-7 ( 0 hom. )

Consequence

SERPINF2
NM_000934.4 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 0.790

Publications

62 publications found

Variant links:

Genes affected

SERPINF2 (HGNC:9075): (serpin family F member 2) This gene encodes a member of the serpin family of serine protease inhibitors. The protein is a major inhibitor of plasmin, which degrades fibrin and various other proteins. Consequently, the proper function of this gene has a major role in regulating the blood clotting pathway. Mutations in this gene result in alpha-2-plasmin inhibitor deficiency, which is characterized by severe hemorrhagic diathesis. Multiple transcript variants encoding different isoforms have been found for this gene. [provided by RefSeq, Sep 2009]

SERPINF2 Gene-Disease associations (from GenCC):

alpha-2-plasmin inhibitor deficiency
Inheritance: AR, AD Classification: DEFINITIVE, STRONG, SUPPORTIVE, LIMITED Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, ClinGen, Ambry Genetics

SERPINF2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.07759318).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_000934.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINF2	NM_000934.4	MANE Select	c.97C>G	p.Arg33Gly	missense	Exon 3 of 10	NP_000925.2	P08697-1
SERPINF2	NM_001165920.1		c.97C>G	p.Arg33Gly	missense	Exon 3 of 10	NP_001159392.1	P08697-1
SERPINF2	NM_001165921.2		c.97C>G	p.Arg33Gly	missense	Exon 3 of 9	NP_001159393.1	P08697-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
SERPINF2	ENST00000453066.6	TSL:5 MANE Select	c.97C>G	p.Arg33Gly	missense	Exon 3 of 10	ENSP00000402286.2	P08697-1
SERPINF2	ENST00000382061.5	TSL:1	c.97C>G	p.Arg33Gly	missense	Exon 3 of 10	ENSP00000371493.4	P08697-1
SERPINF2	ENST00000883620.1		c.97C>G	p.Arg33Gly	missense	Exon 3 of 11	ENSP00000553679.1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD4 exome

AF:

7.07e-7

AC:

AN:

1413466

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

699272

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00

AC:

AN:

32186

American (AMR)

AF:

0.00

AC:

AN:

37290

Ashkenazi Jewish (ASJ)

AF:

0.0000398

AC:

AN:

25130

East Asian (EAS)

AF:

0.00

AC:

AN:

36734

South Asian (SAS)

AF:

0.00

AC:

AN:

81728

European-Finnish (FIN)

AF:

0.00

AC:

AN:

49450

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5548

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

1086986

Other (OTH)

AF:

0.00

AC:

AN:

58414

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.325

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

GnomAD4 genome

Cov.:

Alfa

AF:

0.00

Hom.:

10105

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.068

BayesDel_addAF

Benign

-0.0014

BayesDel_noAF

Benign

-0.24

CADD

Benign

(source)

DANN

Benign

0.40

DEOGEN2

Benign

0.16

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.26

LIST_S2

Benign

0.56

M_CAP

Benign

0.080

MetaRNN

Benign

0.078

MetaSVM

Benign

-0.56

MutationAssessor

Benign

0.55

PhyloP100

0.79

PrimateAI

Benign

0.21

PROVEAN

Benign

-0.52

REVEL

Uncertain

0.30

Sift

Benign

0.31

Sift4G

Benign

0.14

Polyphen

0.020

Vest4

0.13

MutPred

0.20

Loss of solvent accessibility (P = 0.0159)

MVP

0.61

MPC

0.59

ClinPred

0.19

GERP RS

3.0

Varity_R

0.089

gMVP

0.14

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.16

Details are displayed if max score is > 0.2

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

Publications

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

ClinVar

Computational scores

Splicing

Publications

Other links and lift over