chr9-134882587-G-A

Variant names:

• chr9-134882587-G-A
• rs55865317
• NM_004108.3:c.162G>A

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_Strong BP7 BS1 BS2

The NM_004108.3(FCN2):​c.162G>A​(p.Gly54Gly) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00158 in 1,614,160 control chromosomes in the GnomAD database, including 40 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0083 (20 hom., cov: 33)
  • Exomes 𝑓: 0.00088 (20 hom.)
• Consequence: FCN2 NM_004108.3 synonymous
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.365
• Publications: 1 publications found

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

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.55).
• BP7: Synonymous conserved (PhyloP=0.365 with no splicing effect.
• BS1: Variant frequency is greater than expected in population afr. GnomAd4 allele frequency = 0.00834 (1270/152332) while in subpopulation AFR AF = 0.029 (1205/41574). AF 95% confidence interval is 0.0276. There are 20 homozygotes in GnomAd4. There are 609 alleles in the male GnomAd4 subpopulation. Median coverage is 33. This position passed quality control check.
• BS2: High Homozygotes in GnomAd4 at 20 AR gene

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_004108.3. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	NM_004108.3	MANE Select	c.162G>A	p.Gly54Gly	synonymous	Exon 2 of 8	NP_004099.2	Q15485-1
	FCN2	NM_015837.3		c.101-715G>A		intron	N/A	NP_056652.1	Q15485-2

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	ENST00000291744.11	TSL:1 MANE Select	c.162G>A	p.Gly54Gly	synonymous	Exon 2 of 8	ENSP00000291744.6	Q15485-1
	FCN2	ENST00000855732.1		c.162G>A	p.Gly54Gly	synonymous	Exon 2 of 8	ENSP00000525791.1
	FCN2	ENST00000855735.1		c.162G>A	p.Gly54Gly	synonymous	Exon 2 of 8	ENSP00000525794.1

Frequencies

GnomAD3 genomes AF: 0.00834 AC: 1269 AN: 152214 Hom.: 20 Cov.: 33

Gnomad AFR AF: 0.0290

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00288

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.000414

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.000147

Gnomad OTH AF: 0.00431

GnomAD2 exomes AF: 0.00213 AC: 535 AN: 251368 AF XY: 0.00168

Gnomad AFR exome AF: 0.0275

Gnomad AMR exome AF: 0.00197

Gnomad ASJ exome AF: 0.00

Gnomad EAS exome AF: 0.00

Gnomad FIN exome AF: 0.00

Gnomad NFE exome AF: 0.0000616

Gnomad OTH exome AF: 0.00130

GnomAD4 exome AF: 0.000881 AC: 1288 AN: 1461828 Hom.: 20 Cov.: 31 AF XY: 0.000769 AC XY: 559 AN XY: 727216

African (AFR) AF: 0.0299 AC: 1001 AN: 33478

American (AMR) AF: 0.00201 AC: 90 AN: 44722

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 26136

East Asian (EAS) AF: 0.0000252 AC: 1 AN: 39700

South Asian (SAS) AF: 0.000116 AC: 10 AN: 86258

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 53370

Middle Eastern (MID) AF: 0.00173 AC: 10 AN: 5768

European-Non Finnish (NFE) AF: 0.0000315 AC: 35 AN: 1112004

Other (OTH) AF: 0.00233 AC: 141 AN: 60392

GnomAD4 genome AF: 0.00834 AC: 1270 AN: 152332 Hom.: 20 Cov.: 33 AF XY: 0.00818 AC XY: 609 AN XY: 74492

African (AFR) AF: 0.0290 AC: 1205 AN: 41574

American (AMR) AF: 0.00287 AC: 44 AN: 15312

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3472

East Asian (EAS) AF: 0.00 AC: 0 AN: 5186

South Asian (SAS) AF: 0.000414 AC: 2 AN: 4828

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 10624

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 294

European-Non Finnish (NFE) AF: 0.000147 AC: 10 AN: 68020

Other (OTH) AF: 0.00427 AC: 9 AN: 2110

Alfa AF: 0.00378 Hom.: 2

Bravo AF: 0.00933

Asia WGS AF: 0.00318 AC: 11 AN: 3478

EpiCase AF: 0.000164

EpiControl AF: 0.0000593

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.55
CADD	Benign	4.1
DANN	Benign	0.70
PhyloP100		0.36
Mutation Taster		=100/0	polymorphism

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

Other links and lift over

dbSNP: rs55865317; hg19: chr9-137774433;