9-134880832-A-T

Position:

chr9-134880832-A-T

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBS1BS2

The NM_004108.3(FCN2):c.11A>T(p.Asp4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000931 in 1,613,524 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0050 ( 4 hom., cov: 33)

Exomes 𝑓: 0.00051 ( 6 hom. )

Consequence

FCN2
NM_004108.3 missense

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.894

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 -20 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.0037078261).

BP6

Variant 9-134880832-A-T is Benign according to our data. Variant chr9-134880832-A-T is described in ClinVar as [Benign]. Clinvar id is 788558.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00496 (755/152306) while in subpopulation AFR AF= 0.0177 (736/41564). AF 95% confidence interval is 0.0166. There are 4 homozygotes in gnomad4. There are 367 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
FCN2	NM_004108.3 linkuse as main transcript	c.11A>T	p.Asp4Val	missense_variant	1/8	ENST00000291744.11	NP_004099.2	Q15485-1
FCN2	NM_015837.3 linkuse as main transcript	c.11A>T	p.Asp4Val	missense_variant	1/7		NP_056652.1	Q15485-2
FCN2	XM_011518392.4 linkuse as main transcript	c.68-1694A>T		intron_variant			XP_011516694.1
FCN2	XM_006717015.5 linkuse as main transcript	c.68-2470A>T		intron_variant			XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 linkuse as main transcript	c.11A>T	p.Asp4Val	missense_variant	1/8	1	NM_004108.3	ENSP00000291744.6		Q15485-1
FCN2	ENST00000350339.3 linkuse as main transcript	c.11A>T	p.Asp4Val	missense_variant	1/7	5		ENSP00000291741.5		Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.00496

AC:

755

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0178

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000655

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000441

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00114

AC:

285

AN:

249428

Hom.:

AF XY:

0.000807

AC XY:

109

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.0164

Gnomad AMR exome

AF:

0.000464

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00000890

Gnomad OTH exome

AF:

0.000657

GnomAD4 exome

AF:

0.000511

AC:

747

AN:

1461218

Hom.:

Cov.:

AF XY:

0.000437

AC XY:

318

AN XY:

726922

show subpopulations

Gnomad4 AFR exome

AF:

0.0196

Gnomad4 AMR exome

AF:

0.000492

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000270

Gnomad4 OTH exome

AF:

0.000977

GnomAD4 genome

AF:

0.00496

AC:

755

AN:

152306

Hom.:

Cov.:

AF XY:

0.00493

AC XY:

367

AN XY:

74474

show subpopulations

Gnomad4 AFR

AF:

0.0177

Gnomad4 AMR

AF:

0.000654

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000441

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.000917

Hom.:

Bravo

AF:

0.00568

ESP6500AA

AF:

0.0211

AC:

ESP6500EA

AF:

0.00

AC:

ExAC

AF:

0.00160

AC:

194

Asia WGS

AF:

0.000289

AC:

AN:

3478

EpiCase

AF:

0.00

EpiControl

AF:

0.0000593

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 21, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.11

BayesDel_addAF

Benign

-0.54

BayesDel_noAF

Benign

-0.53

CADD

Benign

9.0

DANN

Benign

0.92

DEOGEN2

Benign

0.0063

T;.

Eigen

Benign

-1.0

Eigen_PC

Benign

-1.2

FATHMM_MKL

Benign

0.0039

LIST_S2

Benign

0.59

T;T

MetaRNN

Benign

0.0037

T;T

MetaSVM

Benign

-1.1

MutationAssessor

Benign

1.2

L;L

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-0.73

N;N

REVEL

Benign

0.019

Sift

Uncertain

0.023

D;T

Sift4G

Benign

0.11

T;T

Polyphen

0.39

B;P

Vest4

0.23

MVP

0.38

MPC

0.10

ClinPred

0.0022

GERP RS

-0.59

Varity_R

0.13

gMVP

0.68

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