rs55860122

Variant names:

• chr9-134885891-G-A
• rs55860122
• NM_004108.3:c.553G>A

Your query was ambiguous. Multiple possible variants found:

• chr9-134885891-G-A
• chr9-134885891-G-T

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_004108.3(FCN2):​c.553G>A​(p.Ala185Thr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000521 in 1,612,330 control chromosomes in the GnomAD database, including 1 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/22 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: 𝑓 0.000092 (0 hom., cov: 32)
  • Exomes 𝑓: 0.000048 (1 hom.)
• Consequence: FCN2 NM_004108.3 missense
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.971
• Publications: 6 publications found

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

Our verdict: Likely_benign. The variant received -4 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.044801503).

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004108.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	NM_004108.3	MANE Select	c.553G>A	p.Ala185Thr	missense	Exon 6 of 8	NP_004099.2
	FCN2	NM_015837.3		c.439G>A	p.Ala147Thr	missense	Exon 5 of 7	NP_056652.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	ENST00000291744.11	TSL:1 MANE Select	c.553G>A	p.Ala185Thr	missense	Exon 6 of 8	ENSP00000291744.6
	FCN2	ENST00000855732.1		c.745G>A	p.Ala249Thr	missense	Exon 6 of 8	ENSP00000525791.1
	FCN2	ENST00000855735.1		c.616G>A	p.Ala206Thr	missense	Exon 6 of 8	ENSP00000525794.1

Frequencies

GnomAD3 genomes AF: 0.0000921 AC: 14 AN: 152028 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000585

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000132

Gnomad OTH AF: 0.000480

GnomAD2 exomes AF: 0.0000726 AC: 18 AN: 247902 AF XY: 0.0000969

Gnomad AFR exome AF: 0.00

Gnomad AMR exome AF: 0.00

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.000436

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000718

Gnomad OTH exome AF: 0.00

GnomAD4 exome AF: 0.0000479 AC: 70 AN: 1460302 Hom.: 1 Cov.: 32 AF XY: 0.0000606 AC XY: 44 AN XY: 726422

African (AFR) AF: 0.00 AC: 0 AN: 33470

American (AMR) AF: 0.00 AC: 0 AN: 44602

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 25990

East Asian (EAS) AF: 0.000504 AC: 20 AN: 39692

South Asian (SAS) AF: 0.0000930 AC: 8 AN: 86062

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53162

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 5752

European-Non Finnish (NFE) AF: 0.0000342 AC: 38 AN: 1111258

Other (OTH) AF: 0.0000663 AC: 4 AN: 60314

GnomAD4 genome AF: 0.0000921 AC: 14 AN: 152028 Hom.: 0 Cov.: 32 AF XY: 0.000108 AC XY: 8 AN XY: 74250

African (AFR) AF: 0.00 AC: 0 AN: 41436

American (AMR) AF: 0.00 AC: 0 AN: 15274

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3470

East Asian (EAS) AF: 0.000585 AC: 3 AN: 5132

South Asian (SAS) AF: 0.000207 AC: 1 AN: 4820

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10618

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 316

European-Non Finnish (NFE) AF: 0.000132 AC: 9 AN: 67968

Other (OTH) AF: 0.000480 AC: 1 AN: 2082

Alfa AF: 0.0000283 Hom.: 0

Bravo AF: 0.0000491

ESP6500AA AF: 0.00 AC: 0

ESP6500EA AF: 0.000116 AC: 1

ExAC AF: 0.0000577 AC: 7

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.075
BayesDel_addAF	Benign	-0.62	T
BayesDel_noAF	Benign	-0.79
CADD	Benign	2.0
DANN	Benign	0.88
DEOGEN2	Benign	0.0047	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.020	N
LIST_S2	Benign	0.76	T
M_CAP	Benign	0.0028	T
MetaRNN	Benign	0.045	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.31	N
PhyloP100		-0.97
PrimateAI	Benign	0.31	T
PROVEAN	Benign	-1.1	N
REVEL	Benign	0.0070
Sift	Benign	0.20	T
Sift4G	Benign	0.25	T
Polyphen		0.051	B
Vest4		0.10
MVP		0.23
MPC		0.072
ClinPred		0.0081	T
GERP RS		-3.3
Varity_R		0.15
gMVP		0.077
Mutation Taster		=85/13	polymorphism

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

Other links and lift over

dbSNP: rs55860122; hg19: chr9-137777737; COSMIC: COSV52476166;