rs55895215

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004108.3(FCN2):​c.307C>A​(p.Arg103Ser) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000041 in 1,461,778 control chromosomes in the GnomAD database, with no homozygous occurrence. 13/21 in silico tools predict a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Another variant affecting the same amino acid position, but resulting in a different missense (i.e. R103C) has been classified as Benign.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

FCN2
NM_004108.3 missense

Scores

5
14

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.0660
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Uncertain_significance. Variant got 2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
FCN2NM_004108.3 linkc.307C>A p.Arg103Ser missense_variant Exon 5 of 8 ENST00000291744.11 NP_004099.2 Q15485-1
FCN2NM_015837.3 linkc.193C>A p.Arg65Ser missense_variant Exon 4 of 7 NP_056652.1 Q15485-2
FCN2XM_011518392.4 linkc.274C>A p.Arg92Ser missense_variant Exon 5 of 8 XP_011516694.1
FCN2XM_006717015.5 linkc.160C>A p.Arg54Ser missense_variant Exon 4 of 7 XP_006717078.1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
FCN2ENST00000291744.11 linkc.307C>A p.Arg103Ser missense_variant Exon 5 of 8 1 NM_004108.3 ENSP00000291744.6 Q15485-1
FCN2ENST00000350339.3 linkc.193C>A p.Arg65Ser missense_variant Exon 4 of 7 5 ENSP00000291741.5 Q15485-2

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000410
AC:
6
AN:
1461778
Hom.:
0
Cov.:
32
AF XY:
0.00000550
AC XY:
4
AN XY:
727214
show subpopulations
Gnomad4 AFR exome
AF:
0.00
Gnomad4 AMR exome
AF:
0.00
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.00
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.00000540
Gnomad4 OTH exome
AF:
0.00
GnomAD4 genome
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
AlphaMissense
Benign
0.26
BayesDel_addAF
Benign
-0.097
T
BayesDel_noAF
Benign
-0.38
CADD
Benign
17
DANN
Uncertain
0.98
DEOGEN2
Benign
0.026
T;.
Eigen
Benign
-0.47
Eigen_PC
Benign
-0.72
FATHMM_MKL
Benign
0.011
N
LIST_S2
Benign
0.35
T;T
M_CAP
Benign
0.012
T
MetaRNN
Uncertain
0.45
T;T
MetaSVM
Benign
-0.58
T
MutationAssessor
Benign
1.9
M;.
PrimateAI
Benign
0.32
T
PROVEAN
Uncertain
-3.5
D;D
REVEL
Benign
0.29
Sift
Uncertain
0.0030
D;D
Sift4G
Uncertain
0.011
D;D
Polyphen
0.88
P;P
Vest4
0.43
MutPred
0.51
Gain of glycosylation at R103 (P = 0.0341);.;
MVP
0.81
MPC
0.16
ClinPred
0.72
D
GERP RS
-0.35
Varity_R
0.55
gMVP
0.74

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-137777090; API