rs77862660

Variant names:

• chr9-134882856-T-C
• rs77862660
• NM_004108.3:c.214+217T>C

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_004108.3(FCN2):​c.214+217T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0209 in 152,304 control chromosomes in the GnomAD database, including 166 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 0.021 (166 hom., cov: 33)
• Consequence: FCN2 NM_004108.3 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.462

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 -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.136 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FCN2	NM_004108.3	c.214+217T>C		intron_variant	Intron 2 of 7	ENST00000291744.11	NP_004099.2
FCN2	NM_015837.3	c.101-446T>C		intron_variant	Intron 1 of 6		NP_056652.1
FCN2	XM_011518392.4	c.181+217T>C		intron_variant	Intron 2 of 7		XP_011516694.1
FCN2	XM_006717015.5	c.68-446T>C		intron_variant	Intron 1 of 6		XP_006717078.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FCN2	ENST00000291744.11	c.214+217T>C		intron_variant	Intron 2 of 7	1	NM_004108.3	ENSP00000291744.6
FCN2	ENST00000350339.3	c.101-446T>C		intron_variant	Intron 1 of 6	5		ENSP00000291741.5

Frequencies

GnomAD3 genomes AF: 0.0208 AC: 3170 AN: 152186 Hom.: 162 Cov.: 33

Gnomad AFR AF: 0.0171

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0873

Gnomad ASJ AF: 0.0167

Gnomad EAS AF: 0.144

Gnomad SAS AF: 0.0126

Gnomad FIN AF: 0.0106

Gnomad MID AF: 0.00633

Gnomad NFE AF: 0.00160

Gnomad OTH AF: 0.0181

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

GnomAD4 genome AF: 0.0209 AC: 3181 AN: 152304 Hom.: 166 Cov.: 33 AF XY: 0.0245 AC XY: 1826 AN XY: 74472

Gnomad4 AFR AF: 0.0171

Gnomad4 AMR AF: 0.0879

Gnomad4 ASJ AF: 0.0167

Gnomad4 EAS AF: 0.144

Gnomad4 SAS AF: 0.0126

Gnomad4 FIN AF: 0.0106

Gnomad4 NFE AF: 0.00160

Gnomad4 OTH AF: 0.0175

Alfa AF: 0.00995 Hom.: 7

Bravo AF: 0.0262

Asia WGS AF: 0.0740 AC: 258 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
CADD	Benign	7.1
DANN	Benign	0.72

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.15		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: rs77862660; hg19: chr9-137774702;