9-134885658-G-T

Variant names:

• chr9-134885658-G-T
• rs12684512
• NM_004108.3:c.430-110G>T

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.430-110G>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000303 in 1,320,006 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: 0.0000030 (0 hom.)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.52
• 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=-0.83).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3	c.430-110G>T		intron_variant	Intron 5 of 7	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.316-110G>T		intron_variant	Intron 4 of 6		NP_056652.1
FCN2	XM_011518392.4	c.397-110G>T		intron_variant	Intron 5 of 7		XP_011516694.1
FCN2	XM_006717015.5	c.283-110G>T		intron_variant	Intron 4 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.430-110G>T		intron_variant	Intron 5 of 7	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.316-110G>T		intron_variant	Intron 4 of 6	5		ENSP00000291741.5

Frequencies

GnomAD3 genomes Cov.: 32

GnomAD4 exome AF: 0.00000303 AC: 4 AN: 1320006 Hom.: 0 AF XY: 0.00000152 AC XY: 1 AN XY: 659408

African (AFR) AF: 0.00 AC: 0 AN: 30874

American (AMR) AF: 0.0000955 AC: 4 AN: 41878

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 22898

East Asian (EAS) AF: 0.00 AC: 0 AN: 38588

South Asian (SAS) AF: 0.00 AC: 0 AN: 77716

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 47928

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 4204

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 1000594

Other (OTH) AF: 0.00 AC: 0 AN: 55326

GnomAD4 genome Cov.: 32

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
CADD	Benign	0.80
DANN	Benign	0.76
PhyloP100		-1.5

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs12684512; hg19: chr9-137777504;