1-240092766-ACAGCAGCAGCAG-ACAGCAGCAG

Variant summary

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

The NM_020066.5(FMN2):c.674_676del(p.Gln225del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000564 in 1,455,004 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency:
  • Genomes: 𝑓 0.0 (0 hom., cov: 33)
  • Exomes 𝑓: 0.000056 (0 hom.)
  • Failed GnomAD Quality Control
• Consequence: FMN2 NM_020066.5 inframe_deletion
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.444

Genes affected

FMN2 (HGNC:14074): (formin 2) This gene is a member of the formin homology protein family. The encoded protein is thought to have essential roles in organization of the actin cytoskeleton and in cell polarity. This protein mediates the formation of an actin mesh that positions the spindle during oogenesis and also regulates the formation of actin filaments in the nucleus. This protein also forms a perinuclear actin/focal-adhesion system that regulates the shape and position of the nucleus during cell migration. Mutations in this gene have been associated with infertility and also with an autosomal recessive form of intellectual disability (MRT47). Alternatively spliced transcript variants have been identified. [provided by RefSeq, Jul 2017]

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
FMN2	NM_020066.5	c.674_676del	p.Gln225del	inframe_deletion	1/18	ENST00000319653.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN2	ENST00000319653.14	c.674_676del	p.Gln225del	inframe_deletion	1/18	5	NM_020066.5	P1
FMN2	ENST00000447095.5	c.-87+24710_-87+24712del		intron_variant		3

Frequencies

GnomAD3 genomes AF: 0.00 AC: 0 AN: 151988 Hom.: 0 Cov.: 33 FAILED QC

Gnomad AFR AF: 0.00

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.0000564 AC: 82 AN: 1455004 Hom.: 0 AF XY: 0.0000677 AC XY: 49 AN XY: 723554

Gnomad4 AFR exome AF: 0.00

Gnomad4 AMR exome AF: 0.000273

Gnomad4 ASJ exome AF: 0.000270

Gnomad4 EAS exome AF: 0.0000506

Gnomad4 SAS exome AF: 0.0000817

Gnomad4 FIN exome AF: 0.000192

Gnomad4 NFE exome AF: 0.0000379

Gnomad4 OTH exome AF: 0.0000333

GnomAD4 genome Data not reliable, filtered out with message: AC0 AF: 0.00 AC: 0 AN: 151988 Hom.: 0 Cov.: 33 AF XY: 0.00 AC XY: 0 AN XY: 74244

Gnomad4 AFR AF: 0.00

Gnomad4 AMR AF: 0.00

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.00

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.00

Gnomad4 OTH AF: 0.00

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

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

Publications

LitVar

Other links and lift over

dbSNP: rs532298569; hg19: chr1-240256066;