dbSNP rs1231192657: FMN2:p.Ala603Val (chr1-240177946-C-T) – ACMG Classification: Uncertain_significance (1 pts)

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP4

The NM_020066.5(FMN2):c.1808C>T(p.Ala603Val) variant causes a missense change. The variant allele was found at a frequency of 0.0000132 in 1,439,272 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: not found (cov: 32)

Exomes 𝑓: 0.000013 ( 0 hom. )

Consequence

FMN2
NM_020066.5 missense

Scores

Clinical Significance

Uncertain significance criteria provided, single submitter U:1

Conservation

PhyloP100: 3.99

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:

ENSG00000233735 (HGNC:):

ENSG00000233735 links:

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2

Very rare variant in population databases, with high coverage;

BP4

Computational evidence support a benign effect (MetaRNN=0.38227066).

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN2	NM_020066.5 link	c.1808C>T	p.Ala603Val	missense_variant	Exon 3 of 18	ENST00000319653.14	NP_064450.3	Q9NZ56-1Q9HBL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14 link	c.1808C>T	p.Ala603Val	missense_variant	Exon 3 of 18	5	NM_020066.5	ENSP00000318884.9		Q9NZ56-1

Frequencies

GnomAD3 genomes

Cov.:

GnomAD2 exomes

AF:

0.00000858

AC:

AN:

233092

AF XY:

0.00000794

show subpopulations

Gnomad AFR exome

AF:

0.00

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:

0.0000184

Gnomad OTH exome

AF:

0.00

GnomAD4 exome

AF:

0.0000132

AC:

AN:

1439272

Hom.:

Cov.:

AF XY:

0.00000699

AC XY:

AN XY:

715360

show subpopulations

African (AFR)

AF:

0.00

AC:

AN:

32406

American (AMR)

AF:

0.00

AC:

AN:

39140

Ashkenazi Jewish (ASJ)

AF:

0.00

AC:

AN:

25006

East Asian (EAS)

AF:

0.00

AC:

AN:

39184

South Asian (SAS)

AF:

0.00

AC:

AN:

80874

European-Finnish (FIN)

AF:

0.00

AC:

AN:

52964

Middle Eastern (MID)

AF:

0.00

AC:

AN:

5650

European-Non Finnish (NFE)

AF:

0.0000172

AC:

AN:

1104670

Other (OTH)

AF:

0.00

AC:

AN:

59378

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.491

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

Cov.:

Alfa

AF:

0.00

Hom.:

Bravo

AF:

0.00000378

ClinVar

Significance: Uncertain significance

Submissions summary: Uncertain:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

not specified

Uncertain:1

Aug 22, 2016

Genetic Services Laboratory, University of Chicago

Significance:Uncertain significance

Review Status:criteria provided, single submitter

Collection Method:clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Pathogenic

0.89

BayesDel_addAF

Uncertain

0.075

BayesDel_noAF

Benign

-0.13

CADD

Uncertain

(source)

DANN

Uncertain

0.98

DEOGEN2

Benign

0.26

.;T

Eigen

Pathogenic

0.81

Eigen_PC

Pathogenic

0.79

FATHMM_MKL

Uncertain

0.95

LIST_S2

Benign

0.81

T;T

M_CAP

Benign

0.052

MetaRNN

Benign

0.38

T;T

MetaSVM

Uncertain

0.39

MutationAssessor

Uncertain

2.3

.;M

PhyloP100

4.0

PrimateAI

Uncertain

0.57

PROVEAN

Uncertain

-3.3

D;D

REVEL

Uncertain

0.38

Sift

Uncertain

0.0090

D;D

Sift4G

Pathogenic

0.0

D;D

Polyphen

1.0

.;D

Vest4

0.62

MutPred

0.11

.;Loss of disorder (P = 0.0851);

MVP

0.70

MPC

0.091

ClinPred

0.89

GERP RS

5.5

Varity_R

0.43

gMVP

0.14

Mutation Taster

=65/35

polymorphism

(source)

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.18

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

Transcripts

RefSeq

Ensembl

Frequencies

Age Distribution

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

Other links and lift over