Variant 9-134885372-T-C details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_004108.3(FCN2):c.429+6T>C variant causes a splice region, intron change. The variant allele was found at a frequency of 0.000949 in 1,612,730 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 2/3 splice prediction tools predicting alterations to normal splicing. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0051 ( 5 hom., cov: 33)

Exomes 𝑓: 0.00052 ( 8 hom. )

Consequence

FCN2
NM_004108.3 splice_region, intron

Scores

Splicing: ADA: 0.9754

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: 3.63

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 made for transcript

Verdict is Benign. Variant got -16 ACMG points.

BP6

Variant 9-134885372-T-C is Benign according to our data. Variant chr9-134885372-T-C is described in ClinVar as [Benign]. Clinvar id is 788560.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BS1

Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00513 (778/151768) while in subpopulation AFR AF= 0.0184 (759/41362). AF 95% confidence interval is 0.0173. There are 5 homozygotes in gnomad4. There are 375 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.

BS2

High Homozygotes in GnomAd4 at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	Effect	MANE	Protein	UniProt
FCN2	NM_004108.3 linkuse as main transcript	c.429+6T>C	splice_region_variant, intron_variant	ENST00000291744.11	NP_004099.2	Q15485-1
FCN2	NM_015837.3 linkuse as main transcript	c.315+6T>C	splice_region_variant, intron_variant		NP_056652.1	Q15485-2
FCN2	XM_011518392.4 linkuse as main transcript	c.396+6T>C	splice_region_variant, intron_variant		XP_011516694.1
FCN2	XM_006717015.5 linkuse as main transcript	c.282+6T>C	splice_region_variant, intron_variant		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11 linkuse as main transcript	c.429+6T>C		splice_region_variant, intron_variant		1	NM_004108.3	ENSP00000291744.6		Q15485-1
FCN2	ENST00000350339.3 linkuse as main transcript	c.315+6T>C		splice_region_variant, intron_variant		5		ENSP00000291741.5		Q15485-2

Frequencies

GnomAD3 genomes

AF:

0.00513

AC:

778

AN:

151650

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0184

Gnomad AMI

AF:

0.00

Gnomad AMR

AF:

0.000656

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.00

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.0000442

Gnomad OTH

AF:

0.00288

GnomAD3 exomes

AF:

0.00118

AC:

293

AN:

247370

Hom.:

AF XY:

0.000858

AC XY:

115

AN XY:

134020

show subpopulations

Gnomad AFR exome

AF:

0.0173

Gnomad AMR exome

AF:

0.000467

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:

0.00000896

Gnomad OTH exome

AF:

0.000664

GnomAD4 exome

AF:

0.000515

AC:

753

AN:

1460962

Hom.:

Cov.:

AF XY:

0.000438

AC XY:

318

AN XY:

726774

show subpopulations

Gnomad4 AFR exome

AF:

0.0198

Gnomad4 AMR exome

AF:

0.000493

Gnomad4 ASJ exome

AF:

0.00

Gnomad4 EAS exome

AF:

0.00

Gnomad4 SAS exome

AF:

0.0000348

Gnomad4 FIN exome

AF:

0.00

Gnomad4 NFE exome

AF:

0.00000360

Gnomad4 OTH exome

AF:

0.000945

GnomAD4 genome

AF:

0.00513

AC:

778

AN:

151768

Hom.:

Cov.:

AF XY:

0.00506

AC XY:

375

AN XY:

74158

show subpopulations

Gnomad4 AFR

AF:

0.0184

Gnomad4 AMR

AF:

0.000655

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.00

Gnomad4 NFE

AF:

0.0000442

Gnomad4 OTH

AF:

0.00285

Alfa

AF:

0.00253

Hom.:

Bravo

AF:

0.00584

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	Labcorp Genetics (formerly Invitae), Labcorp	Jul 21, 2017	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.45

CADD

Benign

DANN

Benign

0.91

Splicing

Name

Calibrated prediction

Score

Prediction

dbscSNV1_ADA

Pathogenic

0.98

dbscSNV1_RF

Pathogenic

0.82

SpliceAI score (max)

0.36

Details are displayed if max score is > 0.2

DS_DL_spliceai

0.36

Position offset: -6

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over