rs17549193

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6BA1

The NM_004108.3(FCN2):c.707C>T(p.Thr236Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,613,120 control chromosomes in the GnomAD database, including 64,243 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

Frequency

Genomes: 𝑓 0.29 ( 6900 hom., cov: 32)

Exomes 𝑓: 0.28 ( 57343 hom. )

Consequence

FCN2
NM_004108.3 missense

Scores

Clinical Significance

Benign no assertion criteria provided B:1

Conservation

PhyloP100: -0.351

Publications

60 publications found

Variant links:

Genes affected

FCN2 (HGNC:3624): (ficolin 2) The product of this gene belongs to the ficolin family of proteins. This family is characterized by the presence of a leader peptide, a short N-terminal segment, followed by a collagen-like region, and a C-terminal fibrinogen-like domain. This gene is predominantly expressed in the liver, and has been shown to have carbohydrate binding and opsonic activities. Alternatively spliced transcript variants encoding different isoforms have been identified. [provided by RefSeq, Jul 2008]

FCN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=4.5707822E-4).

BP6

Variant 9-134887180-C-T is Benign according to our data. Variant chr9-134887180-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060333.Status of the report is no_assertion_criteria_provided, 0 stars.

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein
FCN2	NM_004108.3 link	c.707C>T	p.Thr236Met	missense_variant	Exon 8 of 8	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3 link	c.593C>T	p.Thr198Met	missense_variant	Exon 7 of 7		NP_056652.1
FCN2	XM_011518392.4 link	c.674C>T	p.Thr225Met	missense_variant	Exon 8 of 8		XP_011516694.1
FCN2	XM_006717015.5 link	c.560C>T	p.Thr187Met	missense_variant	Exon 7 of 7		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 link	c.707C>T	p.Thr236Met	missense_variant	Exon 8 of 8	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3 link	c.593C>T	p.Thr198Met	missense_variant	Exon 7 of 7	5		ENSP00000291741.5

Frequencies

GnomAD3 genomes

AF:

0.294

AC:

44728

AN:

152002

Hom.:

6888

Cov.:

show subpopulations

Gnomad AFR

AF:

0.346

Gnomad AMI

AF:

0.599

Gnomad AMR

AF:

0.246

Gnomad ASJ

AF:

0.281

Gnomad EAS

AF:

0.0651

Gnomad SAS

AF:

0.280

Gnomad FIN

AF:

0.284

Gnomad MID

AF:

0.348

Gnomad NFE

AF:

0.291

Gnomad OTH

AF:

0.267

GnomAD2 exomes

AF:

0.258

AC:

64816

AN:

251468

AF XY:

0.259

show subpopulations

Gnomad AFR exome

AF:

0.345

Gnomad AMR exome

AF:

0.199

Gnomad ASJ exome

AF:

0.272

Gnomad EAS exome

AF:

0.0554

Gnomad FIN exome

AF:

0.278

Gnomad NFE exome

AF:

0.287

Gnomad OTH exome

AF:

0.263

GnomAD4 exome

AF:

0.277

AC:

403986

AN:

1461000

Hom.:

57343

Cov.:

AF XY:

0.277

AC XY:

201639

AN XY:

726850

show subpopulations

African (AFR)

AF:

0.340

AC:

11382

AN:

33458

American (AMR)

AF:

0.205

AC:

9153

AN:

44724

Ashkenazi Jewish (ASJ)

AF:

0.270

AC:

7042

AN:

26128

East Asian (EAS)

AF:

0.0594

AC:

2357

AN:

39700

South Asian (SAS)

AF:

0.277

AC:

23895

AN:

86240

European-Finnish (FIN)

AF:

0.272

AC:

14507

AN:

53412

Middle Eastern (MID)

AF:

0.285

AC:

1636

AN:

5750

European-Non Finnish (NFE)

AF:

0.286

AC:

317611

AN:

1111220

Other (OTH)

AF:

0.272

AC:

16403

AN:

60368

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.464

Heterozygous variant carriers

16594

33188

49783

66377

82971

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

10368

20736

31104

41472

51840

<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:

0.294

AC:

44773

AN:

152120

Hom.:

6900

Cov.:

AF XY:

0.292

AC XY:

21680

AN XY:

74368

show subpopulations

African (AFR)

AF:

0.347

AC:

14383

AN:

41472

American (AMR)

AF:

0.246

AC:

3767

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.281

AC:

977

AN:

3472

East Asian (EAS)

AF:

0.0647

AC:

335

AN:

5180

South Asian (SAS)

AF:

0.279

AC:

1346

AN:

4830

European-Finnish (FIN)

AF:

0.284

AC:

3011

AN:

10584

Middle Eastern (MID)

AF:

0.340

AC:

100

AN:

294

European-Non Finnish (NFE)

AF:

0.291

AC:

19754

AN:

67976

Other (OTH)

AF:

0.264

AC:

556

AN:

2106

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.502

Heterozygous variant carriers

1614

3228

4843

6457

8071

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

444

888

1332

1776

2220

<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:

0.283

Hom.:

20867

Bravo

AF:

0.289

TwinsUK

AF:

0.279

AC:

1036

ALSPAC

AF:

0.268

AC:

1033

ESP6500AA

AF:

0.340

AC:

1500

ESP6500EA

AF:

0.290

AC:

2495

ExAC

AF:

0.262

AC:

31846

Asia WGS

AF:

0.192

AC:

667

AN:

3478

EpiCase

AF:

0.289

EpiControl

AF:

0.286

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: no assertion criteria provided

LINK: link

Submissions by phenotype

FCN2-related disorder

Benign:1

Nov 01, 2022

PreventionGenetics, part of Exact Sciences

Significance:Benign

Review Status:no assertion criteria provided

Collection Method:clinical testing

This variant is classified as benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.12

BayesDel_addAF

Benign

-0.52

BayesDel_noAF

Benign

-0.37

CADD

Benign

(source)

DANN

Benign

0.95

DEOGEN2

Benign

0.025

T;.

Eigen

Benign

-0.48

Eigen_PC

Benign

-0.63

FATHMM_MKL

Benign

0.21

LIST_S2

Benign

0.83

T;T

MetaRNN

Benign

0.00046

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Uncertain

2.6

M;.

PhyloP100

-0.35

PrimateAI

Benign

0.33

PROVEAN

Uncertain

-2.9

D;D

REVEL

Benign

0.23

Sift

Uncertain

0.0050

D;D

Sift4G

Uncertain

0.047

D;T

Polyphen

0.57

P;P

Vest4

0.045

MPC

0.094

ClinPred

0.025

GERP RS

2.1

Varity_R

0.19

gMVP

0.42

Mutation Taster

=70/30

polymorphism (auto)

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.010

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