rs9283429

Variant names:

• chr1-240398647-C-T
• rs9283429
• NM_020066.5:c.4910+6085C>T

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_001305424.2(FMN2):​c.4922+6085C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0847 in 152,122 control chromosomes in the GnomAD database, including 610 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 0.085 (610 hom., cov: 32)
• Consequence: FMN2 NM_001305424.2 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.120
• Publications: 3 publications found

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]

FMN2 Gene-Disease associations (from GenCC):

• intellectual disability, autosomal recessive 47

  Inheritance: AR Classification: STRONG Submitted by: Ambry Genetics, G2P, Labcorp Genetics (formerly Invitae)
• autosomal recessive non-syndromic intellectual disability

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.89).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.14 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_001305424.2. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	NM_020066.5	MANE Select	c.4910+6085C>T		intron	N/A	NP_064450.3
	FMN2	NM_001305424.2		c.4922+6085C>T		intron	N/A	NP_001292353.1
	FMN2	NM_001348094.2		c.2738+6085C>T		intron	N/A	NP_001335023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	ENST00000319653.14	TSL:5 MANE Select	c.4910+6085C>T		intron	N/A	ENSP00000318884.9
	FMN2	ENST00000679980.1		c.1178+6085C>T		intron	N/A	ENSP00000505449.1
	FMN2	ENST00000681210.1		c.1130+6085C>T		intron	N/A	ENSP00000505131.1

Frequencies

GnomAD3 genomes AF: 0.0847 AC: 12874 AN: 152004 Hom.: 609 Cov.: 32

Gnomad AFR AF: 0.0892

Gnomad AMI AF: 0.0252

Gnomad AMR AF: 0.0781

Gnomad ASJ AF: 0.0619

Gnomad EAS AF: 0.148

Gnomad SAS AF: 0.0402

Gnomad FIN AF: 0.0453

Gnomad MID AF: 0.0854

Gnomad NFE AF: 0.0893

Gnomad OTH AF: 0.101

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

GnomAD4 genome AF: 0.0847 AC: 12883 AN: 152122 Hom.: 610 Cov.: 32 AF XY: 0.0816 AC XY: 6067 AN XY: 74360

African (AFR) AF: 0.0890 AC: 3695 AN: 41498

American (AMR) AF: 0.0779 AC: 1191 AN: 15288

Ashkenazi Jewish (ASJ) AF: 0.0619 AC: 215 AN: 3472

East Asian (EAS) AF: 0.149 AC: 769 AN: 5156

South Asian (SAS) AF: 0.0407 AC: 196 AN: 4820

European-Finnish (FIN) AF: 0.0453 AC: 479 AN: 10578

Middle Eastern (MID) AF: 0.0884 AC: 26 AN: 294

European-Non Finnish (NFE) AF: 0.0893 AC: 6074 AN: 67990

Other (OTH) AF: 0.102 AC: 215 AN: 2114

Alfa AF: 0.0843 Hom.: 476

Bravo AF: 0.0891

Asia WGS AF: 0.0770 AC: 269 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.89
CADD	Benign	4.9
DANN	Benign	0.71
PhyloP100		0.12
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs9283429; hg19: chr1-240561947;