rs1982530

chr1-240135517-T-C

Variant summary

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

The NM_020066.5(FMN2):c.1782+12172T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0879 in 152,220 control chromosomes in the GnomAD database, including 662 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 0.088 (662 hom., cov: 32)
• Consequence: FMN2 NM_020066.5 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.568

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 Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.146 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN2	NM_020066.5	c.1782+12172T>C		intron_variant		ENST00000319653.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN2	ENST00000319653.14	c.1782+12172T>C		intron_variant		5	NM_020066.5	P1

Frequencies

GnomAD3 genomes AF: 0.0879 AC: 13369 AN: 152102 Hom.: 660 Cov.: 32

Gnomad AFR AF: 0.0692

Gnomad AMI AF: 0.0274

Gnomad AMR AF: 0.141

Gnomad ASJ AF: 0.0946

Gnomad EAS AF: 0.116

Gnomad SAS AF: 0.155

Gnomad FIN AF: 0.0750

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0827

Gnomad OTH AF: 0.0982

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

GnomAD4 genome AF: 0.0879 AC: 13383 AN: 152220 Hom.: 662 Cov.: 32 AF XY: 0.0893 AC XY: 6645 AN XY: 74436

Gnomad4 AFR AF: 0.0693

Gnomad4 AMR AF: 0.141

Gnomad4 ASJ AF: 0.0946

Gnomad4 EAS AF: 0.115

Gnomad4 SAS AF: 0.155

Gnomad4 FIN AF: 0.0750

Gnomad4 NFE AF: 0.0828

Gnomad4 OTH AF: 0.0962

Alfa AF: 0.0887 Hom.: 811

Bravo AF: 0.0925

Asia WGS AF: 0.111 AC: 386 AN: 3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
Cadd	Benign	0.85
Dann	Benign	0.23

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: rs1982530; hg19: chr1-240298817;