9-134885244-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BS1 BS2

The NM_004108.3(FCN2):c.307C>T(p.Arg103Cys) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000952 in 1,614,088 control chromosomes in the GnomAD database, including 13 homozygotes. In-silico tool predicts a benign outcome for this variant. 12/20 in silico tools predict 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 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0660

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (MetaRNN=0.006614089).
• BP6: Variant 9-134885244-C-T is Benign according to our data. Variant chr9-134885244-C-T is described in ClinVar as [Benign]. Clinvar id is 788559.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 (781/152310) while in subpopulation AFR AF= 0.0182 (758/41576). AF 95% confidence interval is 0.0172. There are 5 homozygotes in gnomad4. There are 378 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.307C>T	p.Arg103Cys	missense_variant	5/8	ENST00000291744.11
FCN2	NM_015837.3	c.193C>T	p.Arg65Cys	missense_variant	4/7
FCN2	XM_011518392.4	c.274C>T	p.Arg92Cys	missense_variant	5/8
FCN2	XM_006717015.5	c.160C>T	p.Arg54Cys	missense_variant	4/7

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.307C>T	p.Arg103Cys	missense_variant	5/8	1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.193C>T	p.Arg65Cys	missense_variant	4/7	5

Frequencies

GnomAD3 genomes AF: 0.00513 AC: 781 AN: 152192 Hom.: 5 Cov.: 33

Gnomad AFR AF: 0.0183

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000785

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: 0.0000735

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00122 AC: 306 AN: 251124 Hom.: 2 AF XY: 0.000869 AC XY: 118 AN XY: 135782

Gnomad AFR exome AF: 0.0174

Gnomad AMR exome AF: 0.000463

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.0000544

Gnomad SAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000264

Gnomad OTH exome AF: 0.000652

GnomAD4 exome AF: 0.000517 AC: 756 AN: 1461778 Hom.: 8 Cov.: 32 AF XY: 0.000437 AC XY: 318 AN XY: 727214

Gnomad4 AFR exome AF: 0.0198

Gnomad4 AMR exome AF: 0.000492

Gnomad4 ASJ exome AF: 0.00

Gnomad4 EAS exome AF: 0.0000252

Gnomad4 SAS exome AF: 0.0000348

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.00000630

Gnomad4 OTH exome AF: 0.000944

GnomAD4 genome AF: 0.00513 AC: 781 AN: 152310 Hom.: 5 Cov.: 33 AF XY: 0.00508 AC XY: 378 AN XY: 74470

Gnomad4 AFR AF: 0.0182

Gnomad4 AMR AF: 0.000784

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000735

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.00115 Hom.: 2

Bravo AF: 0.00585

ESP6500AA AF: 0.0209 AC: 92

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00169 AC: 205

Asia WGS AF: 0.000289 AC: 1 AN: 3478

EpiCase AF: 0.00

EpiControl AF: 0.0000593

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
AlphaMissense	Benign	0.26
BayesDel_addAF	Benign	-0.45	T
BayesDel_noAF	Benign	-0.40
Cadd	Benign	19
Dann	Uncertain	0.98
DEOGEN2	Benign	0.032	T;.
Eigen	Benign	-0.68
Eigen_PC	Benign	-0.86
FATHMM_MKL	Benign	0.034	N
LIST_S2	Benign	0.14	T;T
MetaRNN	Benign	0.0066	T;T
MetaSVM	Benign	-0.61	T
MutationAssessor	Uncertain	2.6	M;.
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.36	T
PROVEAN	Pathogenic	-5.6	D;D
REVEL	Benign	0.25
Sift	Pathogenic	0.0	D;D
Sift4G	Benign	0.061	T;T
Polyphen		0.38	B;P
Vest4		0.60
MVP		0.81
MPC		0.15
ClinPred		0.059	T
GERP RS		-0.35
Varity_R		0.35
gMVP		0.75

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: rs55895215; hg19: chr9-137777090;