9-134885274-C-T

Variant names:

• chr9-134885274-C-T
• rs17549179
• NM_004108.3:c.337C>T

Variant summary

Our verdict is Benign. The variant received -10 ACMG points: 0P and 10B. BP4_Strong BP6_Moderate BS2

The NM_004108.3(FCN2):​c.337C>T​(p.His113Tyr) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00499 in 1,614,156 control chromosomes in the GnomAD database, including 27 homozygotes. In-silico tool predicts a benign outcome for this variant. 16/21 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0037 (1 hom., cov: 32)
  • Exomes 𝑓: 0.0051 (26 hom.)
• Consequence: FCN2 NM_004108.3 missense
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -1.24
• Publications: 8 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 -10 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.004905343).
• BP6: Variant 9-134885274-C-T is Benign according to our data. Variant chr9-134885274-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2659704.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High Homozygotes in GnomAdExome4 at 26 AR gene

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.337C>T	p.His113Tyr	missense	Exon 5 of 8	NP_004099.2	Q15485-1
	FCN2	NM_015837.3		c.223C>T	p.His75Tyr	missense	Exon 4 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.337C>T	p.His113Tyr	missense	Exon 5 of 8	ENSP00000291744.6	Q15485-1
	FCN2	ENST00000855732.1		c.529C>T	p.His177Tyr	missense	Exon 5 of 8	ENSP00000525791.1
	FCN2	ENST00000855735.1		c.400C>T	p.His134Tyr	missense	Exon 5 of 8	ENSP00000525794.1

Frequencies

GnomAD3 genomes AF: 0.00369 AC: 562 AN: 152202 Hom.: 1 Cov.: 32

Gnomad AFR AF: 0.000868

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00151

Gnomad ASJ AF: 0.00922

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000621

Gnomad FIN AF: 0.0112

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00504

Gnomad OTH AF: 0.00287

GnomAD2 exomes AF: 0.00413 AC: 1038 AN: 251292 AF XY: 0.00417

Gnomad AFR exome AF: 0.00117

Gnomad AMR exome AF: 0.000607

Gnomad ASJ exome AF: 0.00874

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.0137

Gnomad NFE exome AF: 0.00499

Gnomad OTH exome AF: 0.00342

GnomAD4 exome AF: 0.00512 AC: 7491 AN: 1461836 Hom.: 26 Cov.: 32 AF XY: 0.00507 AC XY: 3686 AN XY: 727236

African (AFR) AF: 0.000896 AC: 30 AN: 33478

American (AMR) AF: 0.00110 AC: 49 AN: 44724

Ashkenazi Jewish (ASJ) AF: 0.00915 AC: 239 AN: 26130

East Asian (EAS) AF: 0.00 AC: 0 AN: 39696

South Asian (SAS) AF: 0.000765 AC: 66 AN: 86258

European-Finnish (FIN) AF: 0.0136 AC: 725 AN: 53404

Middle Eastern (MID) AF: 0.000693 AC: 4 AN: 5768

European-Non Finnish (NFE) AF: 0.00546 AC: 6071 AN: 1111984

Other (OTH) AF: 0.00508 AC: 307 AN: 60394

GnomAD4 genome AF: 0.00368 AC: 561 AN: 152320 Hom.: 1 Cov.: 32 AF XY: 0.00368 AC XY: 274 AN XY: 74478

African (AFR) AF: 0.000866 AC: 36 AN: 41586

American (AMR) AF: 0.00150 AC: 23 AN: 15300

Ashkenazi Jewish (ASJ) AF: 0.00922 AC: 32 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5168

South Asian (SAS) AF: 0.000622 AC: 3 AN: 4824

European-Finnish (FIN) AF: 0.0112 AC: 119 AN: 10622

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.00503 AC: 342 AN: 68032

Other (OTH) AF: 0.00284 AC: 6 AN: 2110

Alfa AF: 0.00447 Hom.: 5

Bravo AF: 0.00301

TwinsUK AF: 0.00539 AC: 20

ALSPAC AF: 0.00389 AC: 15

ESP6500AA AF: 0.000227 AC: 1

ESP6500EA AF: 0.00547 AC: 47

ExAC AF: 0.00371 AC: 450

EpiCase AF: 0.00425

EpiControl AF: 0.00397

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.072
BayesDel_addAF	Benign	-0.57	T
BayesDel_noAF	Benign	-0.58
CADD	Benign	1.8
DANN	Benign	0.70
DEOGEN2	Benign	0.017	T
Eigen	Benign	-1.4
Eigen_PC	Benign	-1.5
FATHMM_MKL	Benign	0.033	N
LIST_S2	Benign	0.12	T
MetaRNN	Benign	0.0049	T
MetaSVM	Benign	-0.98	T
MutationAssessor	Benign	0.90	L
PhyloP100		-1.2
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-1.4	N
REVEL	Benign	0.097
Sift	Benign	0.96	T
Sift4G	Benign	0.82	T
Polyphen		0.0	B
Vest4		0.16
MVP		0.46
MPC		0.083
ClinPred		0.0043	T
GERP RS		-5.5
Varity_R		0.16
gMVP		0.60
Mutation Taster		=98/2	polymorphism

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: rs17549179; hg19: chr9-137777120; COSMIC: COSV99391197;