Genetic Variant FCN2:c.429+102C>T (chr9-134885468-C-T) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_004108.3(FCN2):c.429+102C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00588 in 1,525,522 control chromosomes in the GnomAD database, including 425 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.031 ( 219 hom., cov: 32)

Exomes 𝑓: 0.0031 ( 206 hom. )

Consequence

FCN2
NM_004108.3 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -3.12

Publications

1 publications found

Variant links:

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]

FCN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.103 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.429+102C>T		intron	N/A	NP_004099.2	Q15485-1
	FCN2	NM_015837.3		c.315+102C>T		intron	N/A	NP_056652.1	Q15485-2

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FCN2	ENST00000291744.11	TSL:1 MANE Select	c.429+102C>T	intron	N/A	ENSP00000291744.6	Q15485-1
FCN2	ENST00000855732.1		c.621+102C>T	intron	N/A	ENSP00000525791.1
FCN2	ENST00000855735.1		c.492+102C>T	intron	N/A	ENSP00000525794.1

Frequencies

GnomAD3 genomes

AF:

0.0306

AC:

4649

AN:

152004

Hom.:

216

Cov.:

show subpopulations

Gnomad AFR

AF:

0.106

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.0137

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.000387

Gnomad SAS

AF:

0.000832

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00316

Gnomad NFE

AF:

0.000324

Gnomad OTH

AF:

0.0191

GnomAD4 exome

AF:

0.00313

AC:

4295

AN:

1373400

Hom.:

206

AF XY:

0.00268

AC XY:

1815

AN XY:

676596

show subpopulations

African (AFR)

AF:

0.105

AC:

3328

AN:

31622

American (AMR)

AF:

0.00775

AC:

278

AN:

35848

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24256

East Asian (EAS)

AF:

0.0000275

AC:

AN:

36322

South Asian (SAS)

AF:

0.000357

AC:

AN:

78450

European-Finnish (FIN)

AF:

0.00

AC:

AN:

39332

Middle Eastern (MID)

AF:

0.00638

AC:

AN:

4074

European-Non Finnish (NFE)

AF:

0.000145

AC:

155

AN:

1066350

Other (OTH)

AF:

0.00838

AC:

479

AN:

57146

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

Heterozygous variant carriers

195

390

586

781

976

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

104

208

312

416

520

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

AF:

0.0307

AC:

4673

AN:

152122

Hom.:

219

Cov.:

AF XY:

0.0302

AC XY:

2243

AN XY:

74366

show subpopulations

African (AFR)

AF:

0.106

AC:

4395

AN:

41476

American (AMR)

AF:

0.0137

AC:

210

AN:

15298

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3470

East Asian (EAS)

AF:

0.000388

AC:

AN:

5156

South Asian (SAS)

AF:

0.000624

AC:

AN:

4806

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10602

Middle Eastern (MID)

AF:

0.00340

AC:

AN:

294

European-Non Finnish (NFE)

AF:

0.000324

AC:

AN:

67996

Other (OTH)

AF:

0.0189

AC:

AN:

2112

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.503

Heterozygous variant carriers

192

383

575

766

958

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

144

192

240

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

Alfa

AF:

0.0293

Hom.:

122

Bravo

AF:

0.0345

Asia WGS

AF:

0.00808

AC:

AN:

3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

0.10

(source)

DANN

Benign

0.45

PhyloP100

-3.1

Mutation Taster

=100/0

polymorphism (auto)

(source)

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

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Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over