rs28357091

chr9-134887263-GCT-GA

Variant summary

Our verdict is Uncertain significance. Variant got 2 ACMG points: 2P and 0B. PM2

The NM_004108.3(FCN2):c.791_792delinsA(p.Ala264AspfsTer12) variant causes a frameshift change involving the alteration of a non-conserved nucleotide. The variant was absent in control chromosomes in GnomAD project. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. A264A) has been classified as Likely benign.

• Frequency: Genomes: not found (cov: 33)
• Consequence: FCN2 NM_004108.3 frameshift
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.573

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 Uncertain_significance. Variant got 2 ACMG points.

• PM2: Very rare variant in population databases, with high coverage

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FCN2	NM_004108.3	c.791_792delinsA	p.Ala264AspfsTer12	frameshift_variant	8/8	ENST00000291744.11
FCN2	NM_015837.3	c.677_678delinsA	p.Ala226AspfsTer12	frameshift_variant	7/7
FCN2	XM_006717015.5	c.644_645delinsA	p.Ala215AspfsTer12	frameshift_variant	7/7
FCN2	XM_011518392.4	c.758_759delinsA	p.Ala253AspfsTer12	frameshift_variant	8/8

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FCN2	ENST00000291744.11	c.791_792delinsA	p.Ala264AspfsTer12	frameshift_variant	8/8	1	NM_004108.3	P1
FCN2	ENST00000350339.3	c.677_678delinsA	p.Ala226AspfsTer12	frameshift_variant	7/7	5

Frequencies

GnomAD3 genomes Cov.: 33

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome Cov.: 33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

LitVar

Other links and lift over

dbSNP: rs28357091; hg19: chr9-137779110;