9-134885372-T-C

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_Moderate BS1 BS2

The NM_004108.3(FCN2):c.429+6T>C variant causes a splice donor 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. 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_donor_region, intron
• Scores: Splicing: ADA: 0.9754
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 3.63

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

Verdict is Benign. Variant got -10 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_single_submitter, 1 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 GnomAd at 5 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.429+6T>C		splice_donor_region_variant, intron_variant		ENST00000291744.11
FCN2	NM_015837.3	c.315+6T>C		splice_donor_region_variant, intron_variant
FCN2	XM_006717015.5	c.282+6T>C		splice_donor_region_variant, intron_variant
FCN2	XM_011518392.4	c.396+6T>C		splice_donor_region_variant, intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.429+6T>C		splice_donor_region_variant, intron_variant		1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.315+6T>C		splice_donor_region_variant, intron_variant		5

Frequencies

GnomAD3 genomes AF: 0.00513 AC: 778 AN: 151650 Hom.: 5 Cov.: 33

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.: 2 AF XY: 0.000858 AC XY: 115 AN XY: 134020

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.: 8 Cov.: 32 AF XY: 0.000438 AC XY: 318 AN XY: 726774

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.: 5 Cov.: 33 AF XY: 0.00506 AC XY: 375 AN XY: 74158

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.: 1

Bravo AF: 0.00584

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

Invitae

Jul 21, 2017

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.45
Cadd	Benign	14
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

Other links and lift over

dbSNP: rs139943705; hg19: chr9-137777218;