rs17549193

Variant names:

• chr9-134887180-C-T
• rs17549193
• NM_004108.3:c.707C>T

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP6 BA1

The NM_004108.3(FCN2):​c.707C>T​(p.Thr236Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.278 in 1,613,120 control chromosomes in the GnomAD database, including 64,243 homozygotes. In-silico tool predicts a benign outcome for this variant. 14/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (no stars).

• Frequency:
  • Genomes: 𝑓 0.29 (6900 hom., cov: 32)
  • Exomes 𝑓: 0.28 (57343 hom.)
• Consequence: FCN2 NM_004108.3 missense
• Clinical Significance: Benign no assertion criteria provided B:1
• Conservation: PhyloP100: -0.351
• Publications: 61 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: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=4.5707822E-4).
• BP6: Variant 9-134887180-C-T is Benign according to our data. Variant chr9-134887180-C-T is described in ClinVar as Benign. ClinVar VariationId is 3060333.Status of the report is no_assertion_criteria_provided, 0 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.342 is higher than 0.05.

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.707C>T	p.Thr236Met	missense	Exon 8 of 8	NP_004099.2	Q15485-1
	FCN2	NM_015837.3		c.593C>T	p.Thr198Met	missense	Exon 7 of 7	NP_056652.1	Q15485-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	ENST00000291744.11	TSL:1 MANE Select	c.707C>T	p.Thr236Met	missense	Exon 8 of 8	ENSP00000291744.6	Q15485-1
	FCN2	ENST00000855732.1		c.899C>T	p.Thr300Met	missense	Exon 8 of 8	ENSP00000525791.1
	FCN2	ENST00000855735.1		c.770C>T	p.Thr257Met	missense	Exon 8 of 8	ENSP00000525794.1

Frequencies

GnomAD3 genomes AF: 0.294 AC: 44728 AN: 152002 Hom.: 6888 Cov.: 32

Gnomad AFR AF: 0.346

Gnomad AMI AF: 0.599

Gnomad AMR AF: 0.246

Gnomad ASJ AF: 0.281

Gnomad EAS AF: 0.0651

Gnomad SAS AF: 0.280

Gnomad FIN AF: 0.284

Gnomad MID AF: 0.348

Gnomad NFE AF: 0.291

Gnomad OTH AF: 0.267

GnomAD2 exomes AF: 0.258 AC: 64816 AN: 251468 AF XY: 0.259

Gnomad AFR exome AF: 0.345

Gnomad AMR exome AF: 0.199

Gnomad ASJ exome AF: 0.272

Gnomad EAS exome AF: 0.0554

Gnomad FIN exome AF: 0.278

Gnomad NFE exome AF: 0.287

Gnomad OTH exome AF: 0.263

GnomAD4 exome AF: 0.277 AC: 403986 AN: 1461000 Hom.: 57343 Cov.: 36 AF XY: 0.277 AC XY: 201639 AN XY: 726850

African (AFR) AF: 0.340 AC: 11382 AN: 33458

American (AMR) AF: 0.205 AC: 9153 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.270 AC: 7042 AN: 26128

East Asian (EAS) AF: 0.0594 AC: 2357 AN: 39700

South Asian (SAS) AF: 0.277 AC: 23895 AN: 86240

European-Finnish (FIN) AF: 0.272 AC: 14507 AN: 53412

Middle Eastern (MID) AF: 0.285 AC: 1636 AN: 5750

European-Non Finnish (NFE) AF: 0.286 AC: 317611 AN: 1111220

Other (OTH) AF: 0.272 AC: 16403 AN: 60368

GnomAD4 genome AF: 0.294 AC: 44773 AN: 152120 Hom.: 6900 Cov.: 32 AF XY: 0.292 AC XY: 21680 AN XY: 74368

African (AFR) AF: 0.347 AC: 14383 AN: 41472

American (AMR) AF: 0.246 AC: 3767 AN: 15298

Ashkenazi Jewish (ASJ) AF: 0.281 AC: 977 AN: 3472

East Asian (EAS) AF: 0.0647 AC: 335 AN: 5180

South Asian (SAS) AF: 0.279 AC: 1346 AN: 4830

European-Finnish (FIN) AF: 0.284 AC: 3011 AN: 10584

Middle Eastern (MID) AF: 0.340 AC: 100 AN: 294

European-Non Finnish (NFE) AF: 0.291 AC: 19754 AN: 67976

Other (OTH) AF: 0.264 AC: 556 AN: 2106

Alfa AF: 0.283 Hom.: 20867

Bravo AF: 0.289

TwinsUK AF: 0.279 AC: 1036

ALSPAC AF: 0.268 AC: 1033

ESP6500AA AF: 0.340 AC: 1500

ESP6500EA AF: 0.290 AC: 2495

ExAC AF: 0.262 AC: 31846

Asia WGS AF: 0.192 AC: 667 AN: 3478

EpiCase AF: 0.289

EpiControl AF: 0.286

ClinVar

ClinVar submissions

Significance: Benign

Revision: no assertion criteria provided

Pathogenic	VUS	Benign	Condition
-	-	1	FCN2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.12
BayesDel_addAF	Benign	-0.52	T
BayesDel_noAF	Benign	-0.37
CADD	Benign	11
DANN	Benign	0.95
DEOGEN2	Benign	0.025	T
Eigen	Benign	-0.48
Eigen_PC	Benign	-0.63
FATHMM_MKL	Benign	0.21	N
LIST_S2	Benign	0.83	T
MetaRNN	Benign	0.00046	T
MetaSVM	Benign	-1.1	T
MutationAssessor	Uncertain	2.6	M
PhyloP100		-0.35
PrimateAI	Benign	0.33	T
PROVEAN	Uncertain	-2.9	D
REVEL	Benign	0.23
Sift	Uncertain	0.0050	D
Sift4G	Uncertain	0.047	D
Polyphen		0.57	P
Vest4		0.045
MPC		0.094
ClinPred		0.025	T
GERP RS		2.1
Varity_R		0.19
gMVP		0.42
Mutation Taster		=70/30	polymorphism (auto)

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

Other links and lift over

dbSNP: rs17549193; hg19: chr9-137779026; COSMIC: COSV52475907;