Variant 9-134885254-A-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP4_StrongBP6_ModerateBS2

The NM_004108.3(FCN2):c.317A>G(p.Lys106Arg) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000892 in 1,614,052 control chromosomes in the GnomAD database, including 17 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 0.0013 ( 1 hom., cov: 33)

Exomes 𝑓: 0.00085 ( 16 hom. )

Consequence

FCN2
NM_004108.3 missense

Scores

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 1.04

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.006575167).

BP6

Variant 9-134885254-A-G is Benign according to our data. Variant chr9-134885254-A-G is described in ClinVar as [Benign]. Clinvar id is 2659703.Status of the report is criteria_provided_single_submitter, 1 stars.

BS2

High Homozygotes in GnomAdExome at 2 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FCN2	NM_004108.3 linkuse as main transcript	c.317A>G	p.Lys106Arg	missense_variant	5/8	ENST00000291744.11
FCN2	NM_015837.3 linkuse as main transcript	c.203A>G	p.Lys68Arg	missense_variant	4/7
FCN2	XM_011518392.4 linkuse as main transcript	c.284A>G	p.Lys95Arg	missense_variant	5/8
FCN2	XM_006717015.5 linkuse as main transcript	c.170A>G	p.Lys57Arg	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11 linkuse as main transcript	c.317A>G	p.Lys106Arg	missense_variant	5/8	1	NM_004108.3	P1	Q15485-1
FCN2	ENST00000350339.3 linkuse as main transcript	c.203A>G	p.Lys68Arg	missense_variant	4/7	5			Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.00128

AC:

195

AN:

152128

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00169

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00249

Gnomad ASJ

AF:

0.00663

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000208

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.0158

Gnomad NFE

AF:

0.000691

Gnomad OTH

AF:

0.00527

GnomAD3 exomes

AF:

0.00130

AC:

326

AN:

251252

Hom.:

AF XY:

0.00115

AC XY:

156

AN XY:

135838

show subpopulations

Gnomad AFR exome

AF:

0.00160

Gnomad AMR exome

AF:

0.00234

Gnomad ASJ exome

AF:

0.00953

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000261

Gnomad FIN exome

AF:

0.0000463

Gnomad NFE exome

AF:

0.000783

Gnomad OTH exome

AF:

0.00408

GnomAD4 exome

AF:

0.000853

AC:

1247

AN:

1461806

Hom.:

Cov.:

AF XY:

0.000876

AC XY:

637

AN XY:

727222

show subpopulations

Gnomad4 AFR exome

AF:

0.00233

Gnomad4 AMR exome

AF:

0.00284

Gnomad4 ASJ exome

AF:

0.00907

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000325

Gnomad4 FIN exome

AF:

0.0000375

Gnomad4 NFE exome

AF:

0.000475

Gnomad4 OTH exome

AF:

0.00250

GnomAD4 genome

AF:

0.00127

AC:

193

AN:

152246

Hom.:

Cov.:

AF XY:

0.00121

AC XY:

AN XY:

74446

show subpopulations

Gnomad4 AFR

AF:

0.00166

Gnomad4 AMR

AF:

0.00248

Gnomad4 ASJ

AF:

0.00663

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000208

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000691

Gnomad4 OTH

AF:

0.00521

Alfa

AF:

0.00146

Hom.:

Bravo

AF:

0.00173

ESP6500AA

AF:

0.00182

AC:

ESP6500EA

AF:

0.000930

AC:

ExAC

AF:

0.00112

AC:

136

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00158

EpiControl

AF:

0.00124

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2022

FCN2: BP4, BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.084

BayesDel_addAF

Benign

-0.49

BayesDel_noAF

Benign

-0.47

Cadd

Benign

Dann

Benign

0.96

DEOGEN2

Benign

0.0063

T;.

Eigen

Benign

-0.62

Eigen_PC

Benign

-0.61

FATHMM_MKL

Uncertain

0.82

LIST_S2

Benign

0.73

T;T

M_CAP

Benign

0.0086

MetaRNN

Benign

0.0066

T;T

MetaSVM

Benign

-0.82

MutationAssessor

Benign

1.7

L;.

MutationTaster

Benign

0.53

D;N

PrimateAI

Benign

0.32

PROVEAN

Benign

-2.0

N;N

REVEL

Benign

0.10

Sift

Benign

0.18

T;T

Sift4G

Benign

0.18

T;T

Polyphen

0.014

B;B

Vest4

0.14

MVP

0.67

MPC

0.067

ClinPred

0.0048

GERP RS

1.1

Varity_R

0.18

gMVP

0.61

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over