9-134880854-C-T

Variant summary

Our verdict is Benign. Variant got -15 ACMG points: 0P and 15B. BP4_Strong BP6_Moderate BP7 BA1

The NM_004108.3(FCN2):c.33C>T(p.Gly11=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00475 in 1,613,650 control chromosomes in the GnomAD database, including 313 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.025 (154 hom., cov: 33)
  • Exomes 𝑓: 0.0026 (159 hom.)
• Consequence: FCN2 NM_004108.3 synonymous
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.367

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 -15 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.76).
• BP6: Variant 9-134880854-C-T is Benign according to our data. Variant chr9-134880854-C-T is described in ClinVar as [Benign]. Clinvar id is 787074.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-0.367 with no splicing effect.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.0841 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.33C>T	p.Gly11=	synonymous_variant	1/8	ENST00000291744.11
FCN2	NM_015837.3	c.33C>T	p.Gly11=	synonymous_variant	1/7
FCN2	XM_006717015.5	c.68-2448C>T		intron_variant
FCN2	XM_011518392.4	c.68-1672C>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.33C>T	p.Gly11=	synonymous_variant	1/8	1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.33C>T	p.Gly11=	synonymous_variant	1/7	5

Frequencies

GnomAD3 genomes AF: 0.0249 AC: 3792 AN: 152062 Hom.: 155 Cov.: 33

Gnomad AFR AF: 0.0866

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0108

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000207

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.000118

Gnomad OTH AF: 0.0163

GnomAD3 exomes AF: 0.00646 AC: 1613 AN: 249558 Hom.: 67 AF XY: 0.00474 AC XY: 641 AN XY: 135236

Gnomad AFR exome AF: 0.0887

Gnomad AMR exome AF: 0.00414

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad SAS exome AF: 0.0000327

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.000187

Gnomad OTH exome AF: 0.00328

GnomAD4 exome AF: 0.00264 AC: 3863 AN: 1461468 Hom.: 159 Cov.: 33 AF XY: 0.00230 AC XY: 1674 AN XY: 727028

Gnomad4 AFR exome AF: 0.0951

Gnomad4 AMR exome AF: 0.00447

Gnomad4 ASJ exome AF: 0.0000383

Gnomad4 EAS exome AF: 0.0000504

Gnomad4 SAS exome AF: 0.000116

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.0000953

Gnomad4 OTH exome AF: 0.00563

GnomAD4 genome AF: 0.0250 AC: 3799 AN: 152182 Hom.: 154 Cov.: 33 AF XY: 0.0247 AC XY: 1835 AN XY: 74418

Gnomad4 AFR AF: 0.0865

Gnomad4 AMR AF: 0.0108

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.000208

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.000118

Gnomad4 OTH AF: 0.0161

Alfa AF: 0.0100 Hom.: 22

Bravo AF: 0.0289

Asia WGS AF: 0.00433 AC: 15 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.000119

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	-0.76
Cadd	Benign	4.2
Dann	Benign	0.46

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs55797213; hg19: chr9-137772700;