rs2070862

Variant names:

Variant summary

Our verdict is Benign. The variant received -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_000934.4(SERPINF2):c.5C>T(p.Ala2Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.218 in 1,613,214 control chromosomes in the GnomAD database, including 39,047 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.22 ( 3540 hom., cov: 30)

Exomes 𝑓: 0.22 ( 35507 hom. )

Consequence

SERPINF2
NM_000934.4 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -0.488

Publications

39 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: ClinGen, Ambry Genetics, Labcorp Genetics (formerly Invitae), Orphanet

SERPINF2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.001448214).

BP6

Variant 17-1745000-C-T is Benign according to our data. Variant chr17-1745000-C-T is described in ClinVar as Benign. ClinVar VariationId is 256836.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.229 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
SERPINF2	NM_000934.4 link	c.5C>T	p.Ala2Val	missense_variant	Exon 2 of 10	ENST00000453066.6	NP_000925.2

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
SERPINF2	ENST00000453066.6 link	c.5C>T	p.Ala2Val	missense_variant	Exon 2 of 10	5	NM_000934.4	ENSP00000402286.2

Frequencies

GnomAD3 genomes

AF:

0.215

AC:

32669

AN:

151740

Hom.:

3536

Cov.:

show subpopulations

Gnomad AFR

AF:

0.233

Gnomad AMI

AF:

0.0998

Gnomad AMR

AF:

0.208

Gnomad ASJ

AF:

0.132

Gnomad EAS

AF:

0.170

Gnomad SAS

AF:

0.118

Gnomad FIN

AF:

0.194

Gnomad MID

AF:

0.158

Gnomad NFE

AF:

0.227

Gnomad OTH

AF:

0.192

GnomAD2 exomes

AF:

0.202

AC:

50613

AN:

250204

AF XY:

0.197

show subpopulations

Gnomad AFR exome

AF:

0.234

Gnomad AMR exome

AF:

0.217

Gnomad ASJ exome

AF:

0.137

Gnomad EAS exome

AF:

0.176

Gnomad FIN exome

AF:

0.197

Gnomad NFE exome

AF:

0.227

Gnomad OTH exome

AF:

0.204

GnomAD4 exome

AF:

0.218

AC:

318585

AN:

1461356

Hom.:

35507

Cov.:

AF XY:

0.215

AC XY:

156267

AN XY:

726966

show subpopulations

African (AFR)

AF:

0.233

AC:

7815

AN:

33474

American (AMR)

AF:

0.217

AC:

9717

AN:

44706

Ashkenazi Jewish (ASJ)

AF:

0.141

AC:

3675

AN:

26136

East Asian (EAS)

AF:

0.170

AC:

6761

AN:

39698

South Asian (SAS)

AF:

0.121

AC:

10449

AN:

86252

European-Finnish (FIN)

AF:

0.204

AC:

10862

AN:

53194

Middle Eastern (MID)

AF:

0.113

AC:

649

AN:

5726

European-Non Finnish (NFE)

AF:

0.231

AC:

256398

AN:

1111788

Other (OTH)

AF:

0.203

AC:

12259

AN:

60382

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.461

Heterozygous variant carriers

14497

28994

43492

57989

72486

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

8758

17516

26274

35032

43790

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.215

AC:

32704

AN:

151858

Hom.:

3540

Cov.:

AF XY:

0.210

AC XY:

15563

AN XY:

74204

show subpopulations

African (AFR)

AF:

0.233

AC:

9631

AN:

41400

American (AMR)

AF:

0.208

AC:

3165

AN:

15236

Ashkenazi Jewish (ASJ)

AF:

0.132

AC:

458

AN:

3468

East Asian (EAS)

AF:

0.170

AC:

874

AN:

5138

South Asian (SAS)

AF:

0.118

AC:

569

AN:

4824

European-Finnish (FIN)

AF:

0.194

AC:

2047

AN:

10542

Middle Eastern (MID)

AF:

0.153

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.227

AC:

15423

AN:

67944

Other (OTH)

AF:

0.191

AC:

401

AN:

2100

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

1323

2646

3968

5291

6614

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

348

696

1044

1392

1740

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.220

Hom.:

15024

Bravo

AF:

0.221

TwinsUK

AF:

0.264

AC:

979

ALSPAC

AF:

0.238

AC:

919

ESP6500AA

AF:

0.242

AC:

1065

ESP6500EA

AF:

0.221

AC:

1902

ExAC

AF:

0.206

AC:

24982

Asia WGS

AF:

0.158

AC:

553

AN:

3478

EpiCase

AF:

0.210

EpiControl

AF:

0.216

ClinVar

Significance: Benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 12, 2018

GeneDx

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Breakthrough Genomics, Breakthrough Genomics

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.13

BayesDel_addAF

Benign

-0.37

BayesDel_noAF

Benign

-0.17

CADD

Benign

(source)

DANN

Benign

0.94

DEOGEN2

Benign

0.0

.;T;.;.;T

Eigen

Benign

-0.95

Eigen_PC

Benign

-0.86

FATHMM_MKL

Benign

0.054

LIST_S2

Benign

0.50

T;T;T;T;.

MetaRNN

Benign

0.0014

T;T;T;T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

0.0

.;N;N;.;N

PhyloP100

-0.49

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.97

N;N;N;N;N

REVEL

Benign

0.27

Sift

Benign

0.30

T;T;T;D;T

Sift4G

Benign

0.30

T;T;T;T;T

Vest4

0.0

ClinPred

0.0091

GERP RS

-0.87

RBP_binding_hub_radar

0.0

RBP_regulation_power_radar

1.0

Varity_R

0.069

gMVP

0.20

Mutation Taster

=95/5

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over