9-134885468-C-G

Variant names:

• chr9-134885468-C-G
• rs75123259
• NM_004108.3:c.429+102C>G

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2 BP4_Strong

The NM_004108.3(FCN2):​c.429+102C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000000728 in 1,373,420 control chromosomes in the GnomAD database, with no homozygous occurrence. 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: not found (cov: 32)
  • Exomes 𝑓: 7.3e-7 (0 hom.)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -3.12
• Publications: 0 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: Likely_benign. The variant received -2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	NM_004108.3	MANE Select	c.429+102C>G		intron	N/A	NP_004099.2
	FCN2	NM_015837.3		c.315+102C>G		intron	N/A	NP_056652.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FCN2	ENST00000291744.11	TSL:1 MANE Select	c.429+102C>G		intron	N/A	ENSP00000291744.6
	FCN2	ENST00000350339.3	TSL:5	c.315+102C>G		intron	N/A	ENSP00000291741.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 7.28e-7 AC: 1 AN: 1373420 Hom.: 0 AF XY: 0.00000148 AC XY: 1 AN XY: 676606

African (AFR) AF: 0.00 AC: 0 AN: 31638

American (AMR) AF: 0.00 AC: 0 AN: 35848

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 24256

East Asian (EAS) AF: 0.00 AC: 0 AN: 36322

South Asian (SAS) AF: 0.00 AC: 0 AN: 78450

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 39332

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4074

European-Non Finnish (NFE) AF: 9.38e-7 AC: 1 AN: 1066350

Other (OTH) AF: 0.00 AC: 0 AN: 57150

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	0.042
DANN	Benign	0.50
PhyloP100		-3.1

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		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: rs75123259; hg19: chr9-137777314;