Variant rs76267164 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BP4_StrongBS2

The NM_004108.3(FCN2):c.932G>A(p.Arg311Gln) variant causes a missense change. The variant allele was found at a frequency of 0.00481 in 1,613,996 control chromosomes in the GnomAD database, including 57 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as association (★).

Frequency

Genomes: 𝑓 0.0034 ( 5 hom., cov: 33)

Exomes 𝑓: 0.0050 ( 52 hom. )

Consequence

FCN2
NM_004108.3 missense

Scores

Clinical Significance

association criteria provided, single submitter O:1

Conservation

PhyloP100: 6.64

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 made for transcript

Verdict is Benign. Variant got -8 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.012019813).

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN2	NM_004108.3 linkuse as main transcript	c.932G>A	p.Arg311Gln	missense_variant	8/8	ENST00000291744.11	NP_004099.2	Q15485-1
FCN2	NM_015837.3 linkuse as main transcript	c.818G>A	p.Arg273Gln	missense_variant	7/7		NP_056652.1	Q15485-2
FCN2	XM_011518392.4 linkuse as main transcript	c.899G>A	p.Arg300Gln	missense_variant	8/8		XP_011516694.1
FCN2	XM_006717015.5 linkuse as main transcript	c.785G>A	p.Arg262Gln	missense_variant	7/7		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 linkuse as main transcript	c.932G>A	p.Arg311Gln	missense_variant	8/8	1	NM_004108.3	ENSP00000291744.6		Q15485-1
FCN2	ENST00000350339.3 linkuse as main transcript	c.818G>A	p.Arg273Gln	missense_variant	7/7	5		ENSP00000291741.5		Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.00339

AC:

516

AN:

152100

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00109

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00812

Gnomad ASJ

AF:

0.00259

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00891

Gnomad FIN

AF:

0.0000943

Gnomad MID

AF:

0.00633

Gnomad NFE

AF:

0.00410

Gnomad OTH

AF:

0.00624

GnomAD3 exomes

AF:

0.00443

AC:

1111

AN:

250532

Hom.:

AF XY:

0.00472

AC XY:

640

AN XY:

135530

show subpopulations

Gnomad AFR exome

AF:

0.000616

Gnomad AMR exome

AF:

0.00827

Gnomad ASJ exome

AF:

0.00327

Gnomad EAS exome

AF:

0.000163

Gnomad SAS exome

AF:

0.00810

Gnomad FIN exome

AF:

0.000185

Gnomad NFE exome

AF:

0.00410

Gnomad OTH exome

AF:

0.0104

GnomAD4 exome

AF:

0.00496

AC:

7250

AN:

1461780

Hom.:

Cov.:

AF XY:

0.00504

AC XY:

3663

AN XY:

727198

show subpopulations

Gnomad4 AFR exome

AF:

0.000777

Gnomad4 AMR exome

AF:

0.00807

Gnomad4 ASJ exome

AF:

0.00264

Gnomad4 EAS exome

AF:

0.0000252

Gnomad4 SAS exome

AF:

0.00790

Gnomad4 FIN exome

AF:

0.000112

Gnomad4 NFE exome

AF:

0.00520

Gnomad4 OTH exome

AF:

0.00505

GnomAD4 genome

AF:

0.00340

AC:

517

AN:

152216

Hom.:

Cov.:

AF XY:

0.00320

AC XY:

238

AN XY:

74440

show subpopulations

Gnomad4 AFR

AF:

0.00108

Gnomad4 AMR

AF:

0.00817

Gnomad4 ASJ

AF:

0.00259

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00892

Gnomad4 FIN

AF:

0.0000943

Gnomad4 NFE

AF:

0.00410

Gnomad4 OTH

AF:

0.00618

Alfa

AF:

0.00367

Hom.:

Bravo

AF:

0.00402

TwinsUK

AF:

0.00512

AC:

ALSPAC

AF:

0.00545

AC:

ESP6500AA

AF:

0.00113

AC:

ESP6500EA

AF:

0.00384

AC:

ExAC

AF:

0.00446

AC:

542

Asia WGS

AF:

0.00346

AC:

AN:

3478

EpiCase

AF:

0.00463

EpiControl

AF:

0.00409

ClinVar

Significance: association

Submissions summary: Other:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Other:1

association, criteria provided, single submitter

case-control

Population Bio, Inc.

Aug 30, 2022

FCN2 variant c.932G>A (rs76267164) is associated with Progressive multifocal leukoencephalopathy (PML, ORPHA:217260). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.24

BayesDel_addAF

Benign

-0.26

BayesDel_noAF

Benign

-0.15

CADD

Benign

DANN

Pathogenic

1.0

DEOGEN2

Benign

0.085

T;.

Eigen

Uncertain

0.49

Eigen_PC

Uncertain

0.30

FATHMM_MKL

Uncertain

0.92

LIST_S2

Benign

0.82

T;T

MetaRNN

Benign

0.012

T;T

MetaSVM

Uncertain

0.33

MutationAssessor

Pathogenic

3.0

M;.

PrimateAI

Benign

0.35

PROVEAN

Uncertain

-3.2

D;D

REVEL

Uncertain

0.59

Sift

Benign

0.031

D;D

Sift4G

Uncertain

0.0020

D;D

Polyphen

1.0

D;D

Vest4

0.54

MVP

0.80

MPC

0.44

ClinPred

0.041

GERP RS

3.1

Varity_R

0.62

gMVP

0.76

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

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