rs55895215

Variant names:

• chr9-134885244-C-A
• NM_004108.3:c.307C>A

Your query was ambiguous. Multiple possible variants found:

• chr9-134885244-C-A
• chr9-134885244-C-T

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
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.0660

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 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
FCN2	NM_004108.3	c.307C>A	p.Arg103Ser	missense_variant	Exon 5 of 8	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.193C>A	p.Arg65Ser	missense_variant	Exon 4 of 7		NP_056652.1
FCN2	XM_011518392.4	c.274C>A	p.Arg92Ser	missense_variant	Exon 5 of 8		XP_011516694.1
FCN2	XM_006717015.5	c.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
FCN2	ENST00000291744.11	c.307C>A	p.Arg103Ser	missense_variant	Exon 5 of 8	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.193C>A	p.Arg65Ser	missense_variant	Exon 4 of 7	5		ENSP00000291741.5

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

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;