Variant rs55860122 details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 2P and 4B. PM2BP4_Strong

The NM_004108.3(FCN2):c.553G>A(p.Ala185Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,612,330 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.000092 ( 0 hom., cov: 32)

Exomes 𝑓: 0.000048 ( 1 hom. )

Consequence

FCN2
NM_004108.3 missense

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.971

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 -2 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.044801503).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein
FCN2	NM_004108.3 linkuse as main transcript	c.553G>A	p.Ala185Thr	missense_variant	6/8	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3 linkuse as main transcript	c.439G>A	p.Ala147Thr	missense_variant	5/7		NP_056652.1
FCN2	XM_011518392.4 linkuse as main transcript	c.520G>A	p.Ala174Thr	missense_variant	6/8		XP_011516694.1
FCN2	XM_006717015.5 linkuse as main transcript	c.406G>A	p.Ala136Thr	missense_variant	5/7		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 linkuse as main transcript	c.553G>A	p.Ala185Thr	missense_variant	6/8	1	NM_004108.3	ENSP00000291744	P1	Q15485-1
FCN2	ENST00000350339.3 linkuse as main transcript	c.439G>A	p.Ala147Thr	missense_variant	5/7	5		ENSP00000291741		Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.0000921

AC:

AN:

152028

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000585

Gnomad SAS

AF:

0.000207

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.000132

Gnomad OTH

AF:

0.000480

GnomAD3 exomes

AF:

0.0000726

AC:

AN:

247902

Hom.:

AF XY:

0.0000969

AC XY:

AN XY:

134154

show subpopulations

Gnomad AFR exome

AF:

0.00

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000436

Gnomad SAS exome

AF:

0.0000659

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000718

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000479

AC:

AN:

1460302

Hom.:

Cov.:

AF XY:

0.0000606

AC XY:

AN XY:

726422

show subpopulations

Gnomad4 AFR exome

AF:

0.00

Gnomad4 AMR exome

AF:

0.00

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.000504

Gnomad4 SAS exome

AF:

0.0000930

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.0000342

Gnomad4 OTH exome

AF:

0.0000663

GnomAD4 genome

AF:

0.0000921

AC:

AN:

152028

Hom.:

Cov.:

AF XY:

0.000108

AC XY:

AN XY:

74250

show subpopulations

Gnomad4 AFR

AF:

0.00

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.000585

Gnomad4 SAS

AF:

0.000207

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.000132

Gnomad4 OTH

AF:

0.000480

Alfa

AF:

0.0000283

Hom.:

Bravo

AF:

0.0000491

ESP6500AA

AF:

0.00

AC:

ESP6500EA

AF:

0.000116

AC:

ExAC

AF:

0.0000577

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.075

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.79

CADD

Benign

2.0

DANN

Benign

0.88

DEOGEN2

Benign

0.0047

T;.

Eigen

Benign

-1.4

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.020

LIST_S2

Benign

0.76

T;T

M_CAP

Benign

0.0028

MetaRNN

Benign

0.045

T;T

MetaSVM

Benign

-0.98

MutationAssessor

Benign

0.31

N;.

MutationTaster

Benign

1.0

N;N

PrimateAI

Benign

0.31

PROVEAN

Benign

-1.1

N;N

REVEL

Benign

0.0070

Sift

Benign

0.20

T;T

Sift4G

Benign

0.25

T;T

Polyphen

0.051

B;B

Vest4

0.10

MVP

0.23

MPC

0.072

ClinPred

0.0081

GERP RS

-3.3

Varity_R

0.15

gMVP

0.077

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

Computational scores

Splicing

Publications

LitVar

Other links and lift over