9-134883308-G-C

Variant names:

• chr9-134883308-G-C
• rs376263285
• NM_004108.3:c.221G>C

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 2P and 2B. PM2 BP4_Moderate

The NM_004108.3(FCN2):​c.221G>C​(p.Arg74Pro) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. 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: not found (cov: 33)
• Consequence: FCN2 NM_004108.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.24

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]

ACMG classification

Verdict is Uncertain_significance. Variant got 0 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (MetaRNN=0.11189607).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3	c.221G>C	p.Arg74Pro	missense_variant	Exon 3 of 8	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.107G>C	p.Arg36Pro	missense_variant	Exon 2 of 7		NP_056652.1
FCN2	XM_011518392.4	c.188G>C	p.Arg63Pro	missense_variant	Exon 3 of 8		XP_011516694.1
FCN2	XM_006717015.5	c.74G>C	p.Arg25Pro	missense_variant	Exon 2 of 7		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.221G>C	p.Arg74Pro	missense_variant	Exon 3 of 8	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.107G>C	p.Arg36Pro	missense_variant	Exon 2 of 7	5		ENSP00000291741.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome Cov.: 34

GnomAD4 genome Cov.: 33

Bravo AF: 0.00000378

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.083
BayesDel_addAF	Benign	-0.11	T
BayesDel_noAF	Benign	-0.39
CADD	Benign	0.079
DANN	Benign	0.27
DEOGEN2	Benign	0.098	T;.
Eigen	Benign	-1.9
Eigen_PC	Benign	-2.0
FATHMM_MKL	Benign	0.0072	N
LIST_S2	Benign	0.48	T;T
M_CAP	Benign	0.028	D
MetaRNN	Benign	0.11	T;T
MetaSVM	Benign	-0.52	T
MutationAssessor	Benign	0.090	N;.
PrimateAI	Benign	0.47	T
PROVEAN	Benign	-1.2	N;N
REVEL	Benign	0.19
Sift	Benign	0.44	T;T
Sift4G	Benign	0.43	T;T
Polyphen		0.013	B;B
Vest4		0.11
MutPred		0.44		Loss of methylation at R74 (P = 0.0279);.;
MVP		0.59
MPC		0.11
ClinPred		0.049	T
GERP RS		-6.6
Varity_R		0.12
gMVP		0.60

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

Other links and lift over

dbSNP: rs376263285; hg19: chr9-137775154;