Variant 9-134885274-C-T details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -6 ACMG points: 0P and 6B. BP4_StrongBP6_Moderate

The NM_004108.3(FCN2):c.337C>T(p.His113Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,614,156 control chromosomes in the GnomAD database, including 27 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 Likely benign (★). Another nucleotide change resulting in same amino acid change has been previously reported as Likely benignin UniProt.

Frequency

Genomes: 𝑓 0.0037 ( 1 hom., cov: 32)

Exomes 𝑓: 0.0051 ( 26 hom. )

Consequence

FCN2
NM_004108.3 missense

Scores

Clinical Significance

Likely benign criteria provided, single submitter B:1

Conservation

PhyloP100: -1.24

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 Likely_benign. Variant got -6 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.004905343).

BP6

Variant 9-134885274-C-T is Benign according to our data. Variant chr9-134885274-C-T is described in ClinVar as [Likely_benign]. Clinvar id is 2659704.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE
FCN2	NM_004108.3 linkuse as main transcript	c.337C>T	p.His113Tyr	missense_variant	5/8	ENST00000291744.11
FCN2	NM_015837.3 linkuse as main transcript	c.223C>T	p.His75Tyr	missense_variant	4/7
FCN2	XM_011518392.4 linkuse as main transcript	c.304C>T	p.His102Tyr	missense_variant	5/8
FCN2	XM_006717015.5 linkuse as main transcript	c.190C>T	p.His64Tyr	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11 linkuse as main transcript	c.337C>T	p.His113Tyr	missense_variant	5/8	1	NM_004108.3	P1	Q15485-1
FCN2	ENST00000350339.3 linkuse as main transcript	c.223C>T	p.His75Tyr	missense_variant	4/7	5			Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.00369

AC:

562

AN:

152202

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.000868

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00151

Gnomad ASJ

AF:

0.00922

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.000621

Gnomad FIN

AF:

0.0112

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00504

Gnomad OTH

AF:

0.00287

GnomAD3 exomes

AF:

0.00413

AC:

1038

AN:

251292

Hom.:

AF XY:

0.00417

AC XY:

566

AN XY:

135842

show subpopulations

Gnomad AFR exome

AF:

0.00117

Gnomad AMR exome

AF:

0.000607

Gnomad ASJ exome

AF:

0.00874

Gnomad EAS exome

AF:

0.00

Gnomad SAS exome

AF:

0.000849

Gnomad FIN exome

AF:

0.0137

Gnomad NFE exome

AF:

0.00499

Gnomad OTH exome

AF:

0.00342

GnomAD4 exome

AF:

0.00512

AC:

7491

AN:

1461836

Hom.:

Cov.:

AF XY:

0.00507

AC XY:

3686

AN XY:

727236

show subpopulations

Gnomad4 AFR exome

AF:

0.000896

Gnomad4 AMR exome

AF:

0.00110

Gnomad4 ASJ exome

AF:

0.00915

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.000765

Gnomad4 FIN exome

AF:

0.0136

Gnomad4 NFE exome

AF:

0.00546

Gnomad4 OTH exome

AF:

0.00508

GnomAD4 genome

AF:

0.00368

AC:

561

AN:

152320

Hom.:

Cov.:

AF XY:

0.00368

AC XY:

274

AN XY:

74478

show subpopulations

Gnomad4 AFR

AF:

0.000866

Gnomad4 AMR

AF:

0.00150

Gnomad4 ASJ

AF:

0.00922

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.000622

Gnomad4 FIN

AF:

0.0112

Gnomad4 NFE

AF:

0.00503

Gnomad4 OTH

AF:

0.00284

Alfa

AF:

0.00490

Hom.:

Bravo

AF:

0.00301

TwinsUK

AF:

0.00539

AC:

ALSPAC

AF:

0.00389

AC:

ESP6500AA

AF:

0.000227

AC:

ESP6500EA

AF:

0.00547

AC:

ExAC

AF:

0.00371

AC:

450

EpiCase

AF:

0.00425

EpiControl

AF:

0.00397

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not provided

Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Jul 01, 2023

FCN2: BP4 -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.072

BayesDel_addAF

Benign

-0.57

BayesDel_noAF

Benign

-0.58

Cadd

Benign

1.8

Dann

Benign

0.70

DEOGEN2

Benign

0.017

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.033

LIST_S2

Benign

0.12

T;T

MetaRNN

Benign

0.0049

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.90

L;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.40

PROVEAN

Benign

-1.4

N;N

REVEL

Benign

0.097

Sift

Benign

0.96

T;T

Sift4G

Benign

0.82

T;T

Polyphen

0.0

B;B

Vest4

0.16

MVP

0.46

MPC

0.083

ClinPred

0.0043

GERP RS

-5.5

Varity_R

0.16

gMVP

0.60

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

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