chr1-240092803-C-G

Variant names:

Variant summary

Our verdict is Likely benign. The variant received -4 ACMG points: 0P and 4B. BP4_Strong

The NM_001305424.2(FMN2):c.694C>G(p.Pro232Ala) variant causes a missense change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000017 in 1,585,682 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. 14/22 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Uncertain significance (★★). Synonymous variant affecting the same amino acid position (i.e. P232P) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.000026 ( 0 hom., cov: 33)

Exomes 𝑓: 0.000016 ( 0 hom. )

Consequence

FMN2
NM_001305424.2 missense

Scores

Clinical Significance

Uncertain significance criteria provided, multiple submitters, no conflicts U:2

Conservation

PhyloP100: -0.0680

Publications

1 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: Likely_benign. The variant received -4 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.045554787).

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

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein
FMN2	NM_020066.5	MANE Select	c.694C>G	p.Pro232Ala	missense	Exon 1 of 18	NP_064450.3
FMN2	NM_001305424.2		c.694C>G	p.Pro232Ala	missense	Exon 1 of 19	NP_001292353.1
FMN2	NM_001348094.2		c.694C>G	p.Pro232Ala	missense	Exon 1 of 15	NP_001335023.1

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	FMN2	ENST00000319653.14	TSL:5 MANE Select	c.694C>G	p.Pro232Ala	missense	Exon 1 of 18	ENSP00000318884.9
	FMN2	ENST00000447095.5	TSL:3	c.-87+24730C>G		intron	N/A	ENSP00000409308.1

Frequencies

GnomAD3 genomes

AF:

0.0000263

AC:

AN:

152188

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0000965

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

GnomAD2 exomes

AF:

0.0000104

AC:

AN:

192328

AF XY:

0.00000954

show subpopulations

Gnomad AFR exome

AF:

0.000190

Gnomad AMR exome

AF:

0.00

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.00

Gnomad FIN exome

AF:

0.00

Gnomad NFE exome

AF:

0.00

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000160

AC:

AN:

1433494

Hom.:

Cov.:

AF XY:

0.0000239

AC XY:

AN XY:

710634

show subpopulations

African (AFR)

AF:

0.000455

AC:

AN:

32990

American (AMR)

AF:

0.00

AC:

AN:

39794

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25510

East Asian (EAS)

AF:

0.00

AC:

AN:

38424

South Asian (SAS)

AF:

0.00

AC:

AN:

83620

European-Finnish (FIN)

AF:

0.00

AC:

AN:

50040

Middle Eastern (MID)

AF:

0.000588

AC:

AN:

5100

European-Non Finnish (NFE)

AF:

9.10e-7

AC:

AN:

1098726

Other (OTH)

AF:

0.0000675

AC:

AN:

59290

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.445

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:

0.0000263

AC:

AN:

152188

Hom.:

Cov.:

AF XY:

0.0000135

AC XY:

AN XY:

74342

show subpopulations

African (AFR)

AF:

0.0000965

AC:

AN:

41456

American (AMR)

AF:

0.00

AC:

AN:

15290

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

3472

East Asian (EAS)

AF:

0.00

AC:

AN:

5172

South Asian (SAS)

AF:

0.00

AC:

AN:

4836

European-Finnish (FIN)

AF:

0.00

AC:

AN:

10630

Middle Eastern (MID)

AF:

0.00

AC:

AN:

316

European-Non Finnish (NFE)

AF:

0.00

AC:

AN:

68014

Other (OTH)

AF:

0.00

AC:

AN:

2090

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.475

Heterozygous variant carriers

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.0000604

ExAC

AF:

0.00000843

AC:

Asia WGS

AF:

0.000289

AC:

AN:

3478

ClinVar

ClinVar submissions as Germline

Significance:Uncertain significance

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

Inborn genetic diseases (1)

not specified (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.061

BayesDel_addAF

Benign

-0.46

BayesDel_noAF

Benign

-0.61

CADD

Benign

8.4

(source)

DANN

Benign

0.78

DEOGEN2

Benign

0.097

Eigen

Benign

-0.69

Eigen_PC

Benign

-0.71

FATHMM_MKL

Benign

0.037

LIST_S2

Benign

0.43

M_CAP

Benign

0.047

MetaRNN

Benign

0.046

MetaSVM

Benign

-1.0

MutationAssessor

Benign

1.6

PhyloP100

-0.068

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.1

REVEL

Benign

0.033

Sift

Benign

0.25

Sift4G

Benign

0.062

Polyphen

0.075

Vest4

0.15

MutPred

0.17

Loss of glycosylation at P232 (P = 0.018)

MVP

0.30

MPC

0.77

ClinPred

0.050

GERP RS

1.1

Varity_R

0.051

gMVP

0.12

Mutation Taster

=93/7

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

Computational scores

Splicing

Publications

Other links and lift over