9-134880832-A-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.11A>T(p.Asp4Val) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000931 in 1,613,524 control chromosomes in the GnomAD database, including 10 homozygotes. In-silico tool predicts a benign outcome for this variant. 15/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency:
  • Genomes: 𝑓 0.0050 (4 hom., cov: 33)
  • Exomes 𝑓: 0.00051 (6 hom.)
• Consequence: FCN2 NM_004108.3 missense
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.894

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=0.0037078261).
• BP6: Variant 9-134880832-A-T is Benign according to our data. Variant chr9-134880832-A-T is described in ClinVar as [Benign]. Clinvar id is 788558.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00496 (755/152306) while in subpopulation AFR AF= 0.0177 (736/41564). AF 95% confidence interval is 0.0166. There are 4 homozygotes in gnomad4. There are 367 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd at 4 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.11A>T	p.Asp4Val	missense_variant	1/8	ENST00000291744.11
FCN2	NM_015837.3	c.11A>T	p.Asp4Val	missense_variant	1/7
FCN2	XM_006717015.5	c.68-2470A>T		intron_variant
FCN2	XM_011518392.4	c.68-1694A>T		intron_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.11A>T	p.Asp4Val	missense_variant	1/8	1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.11A>T	p.Asp4Val	missense_variant	1/7	5

Frequencies

GnomAD3 genomes AF: 0.00496 AC: 755 AN: 152188 Hom.: 4 Cov.: 33

Gnomad AFR AF: 0.0178

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.000655

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: 0.0000441

Gnomad OTH AF: 0.00287

GnomAD3 exomes AF: 0.00114 AC: 285 AN: 249428 Hom.: 1 AF XY: 0.000807 AC XY: 109 AN XY: 135128

Gnomad AFR exome AF: 0.0164

Gnomad AMR exome AF: 0.000464

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: 0.00000890

Gnomad OTH exome AF: 0.000657

GnomAD4 exome AF: 0.000511 AC: 747 AN: 1461218 Hom.: 6 Cov.: 33 AF XY: 0.000437 AC XY: 318 AN XY: 726922

Gnomad4 AFR exome AF: 0.0196

Gnomad4 AMR exome AF: 0.000492

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: 0.00000270

Gnomad4 OTH exome AF: 0.000977

GnomAD4 genome AF: 0.00496 AC: 755 AN: 152306 Hom.: 4 Cov.: 33 AF XY: 0.00493 AC XY: 367 AN XY: 74474

Gnomad4 AFR AF: 0.0177

Gnomad4 AMR AF: 0.000654

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000441

Gnomad4 OTH AF: 0.00284

Alfa AF: 0.000917 Hom.: 1

Bravo AF: 0.00568

ESP6500AA AF: 0.0211 AC: 93

ESP6500EA AF: 0.00 AC: 0

ExAC AF: 0.00160 AC: 194

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

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
AlphaMissense	Benign	0.11
BayesDel_addAF	Benign	-0.54	T
BayesDel_noAF	Benign	-0.53
Cadd	Benign	9.0
Dann	Benign	0.92
DEOGEN2	Benign	0.0063	T;.
Eigen	Benign	-1.0
Eigen_PC	Benign	-1.2
FATHMM_MKL	Benign	0.0039	N
LIST_S2	Benign	0.59	T;T
MetaRNN	Benign	0.0037	T;T
MetaSVM	Benign	-1.1	T
MutationAssessor	Benign	1.2	L;L
MutationTaster	Benign	1.0	N;N
PrimateAI	Benign	0.40	T
PROVEAN	Benign	-0.73	N;N
REVEL	Benign	0.019
Sift	Uncertain	0.023	D;T
Sift4G	Benign	0.11	T;T
Polyphen		0.39	B;P
Vest4		0.23
MVP		0.38
MPC		0.10
ClinPred		0.0022	T
GERP RS		-0.59
Varity_R		0.13
gMVP		0.68

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: rs61736807; hg19: chr9-137772678;