Genetic Variant FMN2:p.Asp31Gly (chr1-240092201-A-G) – ACMG Classification: Uncertain_significance (0 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 0 ACMG points: 2P and 2B. PM2BP4_Moderate

The NM_020066.5(FMN2):c.92A>G(p.Asp31Gly) variant causes a missense change. The variant allele was found at a frequency of 0.0000723 in 1,562,980 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★).

Frequency

Genomes: 𝑓 0.000048 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000075 ( 0 hom. )

Consequence

FMN2
NM_020066.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 6.44

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

FMN2 links:

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ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 0 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.1287201).

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.92A>G	p.Asp31Gly	missense	Exon 1 of 18	NP_064450.3
FMN2	NM_001305424.2		c.92A>G	p.Asp31Gly	missense	Exon 1 of 19	NP_001292353.1
FMN2	NM_001348094.2		c.92A>G	p.Asp31Gly	missense	Exon 1 of 15	NP_001335023.1

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	ENST00000319653.14	TSL:5 MANE Select	c.92A>G	p.Asp31Gly	missense	Exon 1 of 18	ENSP00000318884.9	Q9NZ56-1
	FMN2	ENST00000447095.5	TSL:3	c.-87+24128A>G		intron	N/A	ENSP00000409308.1	B0QZA8

Frequencies

GnomAD3 genomes

AF:

0.0000478

AC:

AN:

146534

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000252

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:

0.0000901

Gnomad OTH

AF:

0.00

GnomAD2 exomes

AF:

0.0000411

AC:

AN:

194760

AF XY:

0.0000566

show subpopulations

Gnomad AFR exome

AF:

0.000188

Gnomad AMR exome

AF:

0.0000338

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.0000482

Gnomad OTH exome

AF:

0.000200

GnomAD4 exome

AF:

0.0000748

AC:

106

AN:

1416446

Hom.:

Cov.:

AF XY:

0.0000642

AC XY:

AN XY:

701042

show subpopulations

African (AFR)

AF:

0.0000610

AC:

AN:

32774

American (AMR)

AF:

0.00

AC:

AN:

40180

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

24688

East Asian (EAS)

AF:

0.00

AC:

AN:

38200

South Asian (SAS)

AF:

0.00

AC:

AN:

81794

European-Finnish (FIN)

AF:

0.00

AC:

AN:

47686

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5244

European-Non Finnish (NFE)

AF:

0.0000901

AC:

AN:

1087580

Other (OTH)

AF:

0.000103

AC:

AN:

58300

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.488

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

AF:

0.0000478

AC:

AN:

146534

Hom.:

Cov.:

AF XY:

0.0000561

AC XY:

AN XY:

71264

show subpopulations

African (AFR)

AF:

0.0000252

AC:

AN:

39694

American (AMR)

AF:

0.00

AC:

AN:

14806

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3410

East Asian (EAS)

AF:

0.00

AC:

AN:

4842

South Asian (SAS)

AF:

0.00

AC:

AN:

4558

European-Finnish (FIN)

AF:

0.00

AC:

AN:

9444

Middle Eastern (MID)

AF:

0.00

AC:

AN:

304

European-Non Finnish (NFE)

AF:

0.0000901

AC:

AN:

66576

Other (OTH)

AF:

0.00

AC:

AN:

2014

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.525

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome 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

Alfa

AF:

0.0000455

Hom.:

Bravo

AF:

0.0000227

ExAC

AF:

0.0000423

AC:

ClinVar

ClinVar submissions

Significance:Uncertain significance

Revision:criteria provided, single submitter

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Uncertain

0.36

BayesDel_addAF

Benign

-0.32

BayesDel_noAF

Benign

-0.42

CADD

Uncertain

(source)

DANN

Benign

0.76

DEOGEN2

Benign

0.38

Eigen

Benign

-0.24

Eigen_PC

Benign

-0.17

FATHMM_MKL

Benign

0.50

LIST_S2

Benign

0.57

M_CAP

Benign

0.080

MetaRNN

Benign

0.13

MetaSVM

Benign

-0.99

MutationAssessor

Benign

1.8

PhyloP100

6.4

PrimateAI

Pathogenic

0.90

PROVEAN

Uncertain

-4.0

REVEL

Benign

0.12

Sift

Uncertain

0.0010

Sift4G

Uncertain

0.0090

Polyphen

0.024

Vest4

0.22

MutPred

0.076

Gain of MoRF binding (P = 0.0369)

MVP

0.35

MPC

1.0

ClinPred

0.20

GERP RS

3.9

PromoterAI

0.033

Neutral

(source)

Varity_R

0.55

gMVP

0.14

Mutation Taster

=91/9

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

Age Distribution

ClinVar

Computational scores

Splicing

Publications

Other links and lift over