NM_020066.5:c.3174T>A

Variant names:

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4_StrongBP6_Very_StrongBP7

The NM_020066.5(FMN2):c.3174T>A(p.Leu1058Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 1)

Exomes 𝑓: 0.00093 ( 0 hom. )

Failed GnomAD Quality Control

Consequence

FMN2
NM_020066.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -8.07

Publications

0 publications found

Variant links:

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

FMN2 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Benign. The variant received -13 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-1.02).

BP6

Variant 1-240207986-T-A is Benign according to our data. Variant chr1-240207986-T-A is described in ClinVar as Likely_benign. ClinVar VariationId is 435229.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-8.07 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020066.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FMN2	NM_020066.5	MANE Select	c.3174T>A	p.Leu1058Leu	synonymous	Exon 5 of 18	NP_064450.3
FMN2	NM_001305424.2		c.3186T>A	p.Leu1062Leu	synonymous	Exon 6 of 19	NP_001292353.1
FMN2	NM_001348094.2		c.1986+19724T>A		intron	N/A	NP_001335023.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FMN2	ENST00000319653.14	TSL:5 MANE Select	c.3174T>A	p.Leu1058Leu	synonymous	Exon 5 of 18	ENSP00000318884.9
FMN2	ENST00000679980.1		c.188+994T>A		intron	N/A	ENSP00000505449.1
FMN2	ENST00000681210.1		c.285+19724T>A		intron	N/A	ENSP00000505131.1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

AN:

3806

Hom.:

Cov.:

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 NFE

AF:

0.00

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.000807

AC:

AN:

13632

AF XY:

0.000761

show subpopulations

Gnomad AFR exome

AF:

0.0113

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.0122

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.000545

Gnomad OTH exome

AF:

0.0127

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000935

AC:

108

AN:

115560

Hom.:

Cov.:

AF XY:

0.000950

AC XY:

AN XY:

63138

show subpopulations

⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.

African (AFR)

AF:

0.00209

AC:

AN:

2388

American (AMR)

AF:

0.00

AC:

AN:

4130

Ashkenazi Jewish (ASJ)

AF:

0.00185

AC:

AN:

2162

East Asian (EAS)

AF:

0.000788

AC:

AN:

3806

South Asian (SAS)

AF:

0.000308

AC:

AN:

19478

European-Finnish (FIN)

AF:

0.000272

AC:

AN:

14692

Middle Eastern (MID)

AF:

0.00

AC:

AN:

336

European-Non Finnish (NFE)

AF:

0.00120

AC:

AN:

63372

Other (OTH)

AF:

0.00192

AC:

AN:

5196

⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.350

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Variant carriers

<30

30-35

35-40

40-45

45-50

50-55

55-60

60-65

65-70

70-75

75-80

>80

Age

GnomAD4 genome

Data not reliable, filtered out with message: AC0;AS_VQSR

AF:

0.00

AC:

AN:

3806

Hom.:

Cov.:

AF XY:

0.00

AC XY:

AN XY:

2000

African (AFR)

AF:

0.00

AC:

AN:

576

American (AMR)

AF:

0.00

AC:

AN:

472

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

150

East Asian (EAS)

AF:

0.00

AC:

AN:

South Asian (SAS)

AF:

0.00

AC:

AN:

European-Finnish (FIN)

AF:

0.00

AC:

AN:

210

Middle Eastern (MID)

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

2210

Other (OTH)

AF:

0.00

AC:

AN:

Alfa

AF:

0.00155

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Sep 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FMN2: BP4, BP7

Breakthrough Genomics, Breakthrough Genomics

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:not provided

not specified

Benign:1

Sep 18, 2015

Genetic Services Laboratory, University of Chicago

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

FMN2-related disorder

Benign:1

May 13, 2020

PreventionGenetics, part of Exact Sciences

Significance:Likely benign

Review Status:criteria provided, single submitter

Collection Method:clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications).

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-1.0

CADD

Benign

0.60

(source)

DANN

Benign

0.51

PhyloP100

-8.1

Mutation Taster

=99/1

polymorphism

(source)

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

You must be logged in to view publications. This limit was set because tens of millions (!) of queries from AI bots are generated daily.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

Publications

ACMG classification

Variant Effect in Transcripts

RefSeq Transcripts

Ensembl Transcripts

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over