rs772906937

Variant names:

• chr9-134885242-C-G
• rs772906937
• NM_004108.3:c.305C>G

Your query was ambiguous. Multiple possible variants found:

• chr9-134885242-C-G
• chr9-134885242-C-T

Variant summary

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

The NM_004108.3(FCN2):​c.305C>G​(p.Pro102Arg) 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 1,461,770 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: 0.480

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.305C>G	p.Pro102Arg	missense_variant	Exon 5 of 8	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.191C>G	p.Pro64Arg	missense_variant	Exon 4 of 7		NP_056652.1
FCN2	XM_011518392.4	c.272C>G	p.Pro91Arg	missense_variant	Exon 5 of 8		XP_011516694.1
FCN2	XM_006717015.5	c.158C>G	p.Pro53Arg	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.305C>G	p.Pro102Arg	missense_variant	Exon 5 of 8	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.191C>G	p.Pro64Arg	missense_variant	Exon 4 of 7	5		ENSP00000291741.5

Frequencies

GnomAD3 genomes Cov.: 33

GnomAD3 exomes AF: 0.00000796 AC: 2 AN: 251102 Hom.: 0 AF XY: 0.00000737 AC XY: 1 AN XY: 135768

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.0000578

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.00

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.00000137 AC: 2 AN: 1461770 Hom.: 0 Cov.: 32 AF XY: 0.00000138 AC XY: 1 AN XY: 727210

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.0000447

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: 0.00

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	0.17
BayesDel_addAF	Benign	-0.31	T
BayesDel_noAF	Benign	-0.50
CADD	Benign	19
DANN	Uncertain	1.0
DEOGEN2	Benign	0.054	T;.
Eigen	Uncertain	0.19
Eigen_PC	Benign	-0.12
FATHMM_MKL	Benign	0.17	N
LIST_S2	Uncertain	0.87	D;D
M_CAP	Benign	0.010	T
MetaRNN	Uncertain	0.60	D;D
MetaSVM	Benign	-0.79	T
MutationAssessor	Pathogenic	3.4	M;.
PrimateAI	Benign	0.46	T
PROVEAN	Pathogenic	-4.7	D;D
REVEL	Benign	0.092
Sift	Uncertain	0.0030	D;D
Sift4G	Uncertain	0.0060	D;D
Polyphen		1.0	D;D
Vest4		0.39
MutPred		0.65		Gain of solvent accessibility (P = 0.0411);.;
MVP		0.65
MPC		0.43
ClinPred		0.73	D
GERP RS		2.6
Varity_R		0.51
gMVP		0.71

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs772906937; hg19: chr9-137777088;