9-134887306-G-T

Variant summary

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

The NM_004108.3(FCN2):c.833G>T(p.Arg278Leu) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000137 in 1,461,880 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: not found (cov: 33)
  • Exomes 𝑓: 0.0000014 (0 hom.)
• Consequence: FCN2 NM_004108.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.12

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=0.13072035).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.833G>T	p.Arg278Leu	missense_variant	8/8	ENST00000291744.11
FCN2	NM_015837.3	c.719G>T	p.Arg240Leu	missense_variant	7/7
FCN2	XM_011518392.4	c.800G>T	p.Arg267Leu	missense_variant	8/8
FCN2	XM_006717015.5	c.686G>T	p.Arg229Leu	missense_variant	7/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.833G>T	p.Arg278Leu	missense_variant	8/8	1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.719G>T	p.Arg240Leu	missense_variant	7/7	5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461880 Hom.: 0 Cov.: 35 AF XY: 0.00 AC XY: 0 AN XY: 727242

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: 0.00000180

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	0.091
BayesDel_addAF	Benign	-0.24	T
BayesDel_noAF	Benign	-0.59
Cadd	Benign	0.21
Dann	Benign	0.16
DEOGEN2	Benign	0.0022	T;.
Eigen	Benign	-1.7
Eigen_PC	Benign	-1.7
FATHMM_MKL	Benign	0.018	N
LIST_S2	Benign	0.70	T;T
M_CAP	Benign	0.016	T
MetaRNN	Benign	0.13	T;T
MetaSVM	Benign	-0.88	T
MutationAssessor	Benign	-0.24	N;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.27	T
PROVEAN	Benign	0.96	N;N
REVEL	Benign	0.21
Sift	Benign	1.0	T;T
Sift4G	Benign	1.0	T;T
Polyphen		0.0010	B;B
Vest4		0.094
MutPred		0.61		Loss of MoRF binding (P = 0.0095);.;
MVP		0.44
MPC		0.087
ClinPred		0.029	T
GERP RS		-6.5
Varity_R		0.14
gMVP		0.61

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: rs147553607; hg19: chr9-137779152;