dbSNP rs61736807: FCN2:p.Asp4Gly (chr9-134880832-A-G) – ACMG Classification: Likely_benign (-2 pts)

Variant summary

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

The NM_004108.3(FCN2):c.11A>G(p.Asp4Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000657 in 152,310 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 16/21 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 0.0000066 ( 0 hom., cov: 33)

Consequence

FCN2
NM_004108.3 missense

Scores

Clinical Significance

Not reported in ClinVar

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:

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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=0.034161747).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3 link	c.11A>G	p.Asp4Gly	missense_variant	Exon 1 of 8	ENST00000291744.11	NP_004099.2	Q15485-1
FCN2	NM_015837.3 link	c.11A>G	p.Asp4Gly	missense_variant	Exon 1 of 7		NP_056652.1	Q15485-2
FCN2	XM_011518392.4 link	c.68-1694A>G		intron_variant	Intron 1 of 7		XP_011516694.1
FCN2	XM_006717015.5 link	c.68-2470A>G		intron_variant	Intron 1 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 link	c.11A>G	p.Asp4Gly	missense_variant	Exon 1 of 8	1	NM_004108.3	ENSP00000291744.6		Q15485-1
FCN2	ENST00000350339.3 link	c.11A>G	p.Asp4Gly	missense_variant	Exon 1 of 7	5		ENSP00000291741.5		Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.00000657

AC:

AN:

152192

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000241

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.00

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:

0.00

Gnomad OTH

AF:

0.00

GnomAD3 exomes

AF:

0.00000401

AC:

AN:

249428

Hom.:

AF XY:

0.00

AC XY:

AN XY:

135128

show subpopulations

Gnomad AFR exome

AF:

0.0000621

Gnomad AMR exome

AF:

0.00

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:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

Cov.:

GnomAD4 genome

AF:

0.00000657

AC:

AN:

152310

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

74476

show subpopulations

Gnomad4 AFR

AF:

0.0000241

Gnomad4 AMR

AF:

0.00

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.00

Gnomad4 OTH

AF:

0.00

ExAC

AF:

0.00000824

AC:

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.35

BayesDel_noAF

Benign

-0.56

CADD

Benign

8.1

DANN

Benign

0.60

DEOGEN2

Benign

0.0044

T;.

Eigen

Benign

-1.3

Eigen_PC

Benign

-1.4

FATHMM_MKL

Benign

0.00038

LIST_S2

Benign

0.48

T;T

M_CAP

Benign

0.016

MetaRNN

Benign

0.034

T;T

MetaSVM

Benign

-1.0

MutationAssessor

Benign

0.55

N;N

PrimateAI

Benign

0.41

PROVEAN

Benign

0.090

N;N

REVEL

Benign

0.068

Sift

Benign

0.51

T;T

Sift4G

Benign

0.84

T;T

Polyphen

0.0

B;B

Vest4

0.10

MutPred

0.19

Loss of helix (P = 0.0167);Loss of helix (P = 0.0167);

MVP

0.28

MPC

0.094

ClinPred

0.012

GERP RS

-0.59

Varity_R

0.046

gMVP

0.66

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