9-134887405-G-C

Variant names:

• chr9-134887405-G-C
• NM_004108.3:c.932G>C

Variant summary

Our verdict is Uncertain significance. Variant got 4 ACMG points: 4P and 0B. PM2 PP3_Moderate

The NM_004108.3(FCN2):​c.932G>C​(p.Arg311Pro) variant causes a missense change. The variant allele was found at a frequency of 0.000000684 in 1,461,794 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a pathogenic 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. R311Q) has been classified as Uncertain significance.

• Frequency:
  • Genomes: not found (cov: 33)
  • Exomes 𝑓: 6.8e-7 (0 hom.)
• Consequence: FCN2 NM_004108.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 6.64

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 4 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• PP3: MetaRNN computational evidence supports a deleterious effect, 0.936

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3	c.932G>C	p.Arg311Pro	missense_variant	Exon 8 of 8	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.818G>C	p.Arg273Pro	missense_variant	Exon 7 of 7		NP_056652.1
FCN2	XM_011518392.4	c.899G>C	p.Arg300Pro	missense_variant	Exon 8 of 8		XP_011516694.1
FCN2	XM_006717015.5	c.785G>C	p.Arg262Pro	missense_variant	Exon 7 of 7		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.932G>C	p.Arg311Pro	missense_variant	Exon 8 of 8	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.818G>C	p.Arg273Pro	missense_variant	Exon 7 of 7	5		ENSP00000291741.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 6.84e-7 AC: 1 AN: 1461794 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727204

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: 8.99e-7

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	Pathogenic	0.93
BayesDel_addAF	Pathogenic	0.21	D
BayesDel_noAF	Uncertain	0.060
CADD	Benign	23
DANN	Uncertain	0.99
DEOGEN2	Benign	0.23	T;.
Eigen	Uncertain	0.60
Eigen_PC	Uncertain	0.38
FATHMM_MKL	Pathogenic	0.97	D
LIST_S2	Benign	0.83	T;T
M_CAP	Uncertain	0.11	D
MetaRNN	Pathogenic	0.94	D;D
MetaSVM	Uncertain	0.60	D
MutationAssessor	Pathogenic	4.6	H;.
PrimateAI	Benign	0.42	T
PROVEAN	Pathogenic	-6.0	D;D
REVEL	Pathogenic	0.66
Sift	Uncertain	0.0010	D;D
Sift4G	Pathogenic	0.0010	D;D
Polyphen		1.0	D;D
Vest4		0.69
MutPred		0.79		Loss of MoRF binding (P = 0);.;
MVP		0.87
MPC		0.50
ClinPred		0.99	D
GERP RS		3.1
Varity_R		0.99
gMVP		0.96

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

No publications associated with this variant yet.

Other links and lift over

hg19: chr9-137779251;