rs188083977

Variant names:

Your query was ambiguous. Multiple possible variants found:

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.2823A>C(p.Gly941Gly) 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 0.0072 ( 0 hom., cov: 0)

Exomes 𝑓: 0.00099 ( 12 hom. )

Failed GnomAD Quality Control

Consequence

FMN2
NM_020066.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.845

Publications

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

FMN2 links:

Genome browser will be placed here

new If you want to explore the variant's impact on the transcript NM_020066.5, check out the Mutation Effect Viewer. This is especially useful for frameshift variants or if you want to visualize the effect of exon loss / intron retention.

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=-0.91).

BP6

Variant 1-240207635-A-C is Benign according to our data. Variant chr1-240207635-A-C is described in ClinVar as Likely_benign. ClinVar VariationId is 435227.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-0.845 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.2823A>C	p.Gly941Gly	synonymous	Exon 5 of 18	NP_064450.3
FMN2	NM_001305424.2		c.2835A>C	p.Gly945Gly	synonymous	Exon 6 of 19	NP_001292353.1
FMN2	NM_001348094.2		c.1986+19373A>C		intron	N/A	NP_001335023.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
FMN2	ENST00000319653.14	TSL:5 MANE Select	c.2823A>C	p.Gly941Gly	synonymous	Exon 5 of 18	ENSP00000318884.9	Q9NZ56-1
FMN2	ENST00000679980.1		c.188+643A>C		intron	N/A	ENSP00000505449.1	A0A7P0T994
FMN2	ENST00000681210.1		c.285+19373A>C		intron	N/A	ENSP00000505131.1	A0A7P0Z432

Frequencies

GnomAD3 genomes

AF:

0.00728

AC:

312

AN:

42832

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00942

Gnomad AMI

AF:

0.0108

Gnomad AMR

AF:

0.00633

Gnomad ASJ

AF:

0.00643

Gnomad EAS

AF:

0.00923

Gnomad SAS

AF:

0.00835

Gnomad FIN

AF:

0.00998

Gnomad MID

AF:

0.0400

Gnomad NFE

AF:

0.00610

Gnomad OTH

AF:

0.00530

GnomAD2 exomes

AF:

0.000548

AC:

116

AN:

211838

AF XY:

0.000504

show subpopulations

Gnomad AFR exome

AF:

0.000227

Gnomad AMR exome

AF:

0.000413

Gnomad ASJ exome

AF:

0.00

Gnomad EAS exome

AF:

0.000339

Gnomad FIN exome

AF:

0.000207

Gnomad NFE exome

AF:

0.000757

Gnomad OTH exome

AF:

0.00142

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.000989

AC:

856

AN:

865086

Hom.:

Cov.:

AF XY:

0.000961

AC XY:

407

AN XY:

423356

show subpopulations

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

African (AFR)

AF:

0.00102

AC:

AN:

14740

American (AMR)

AF:

0.00137

AC:

AN:

27094

Ashkenazi Jewish (ASJ)

AF:

0.00170

AC:

AN:

8822

East Asian (EAS)

AF:

0.00180

AC:

AN:

12226

South Asian (SAS)

AF:

0.00213

AC:

AN:

43092

European-Finnish (FIN)

AF:

0.00118

AC:

AN:

24574

Middle Eastern (MID)

AF:

0.00152

AC:

AN:

1974

European-Non Finnish (NFE)

AF:

0.000844

AC:

593

AN:

702530

Other (OTH)

AF:

0.00166

AC:

AN:

30034

⚠️ 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: 0.385

Heterozygous variant carriers

108

161

215

269

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Exome Het

Exome Hom

Variant carriers

100

<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: AS_VQSR

AF:

0.00724

AC:

310

AN:

42846

Hom.:

Cov.:

AF XY:

0.00747

AC XY:

154

AN XY:

20626

show subpopulations

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

African (AFR)

AF:

0.00939

AC:

AN:

9048

American (AMR)

AF:

0.00633

AC:

AN:

4424

Ashkenazi Jewish (ASJ)

AF:

0.00643

AC:

AN:

778

East Asian (EAS)

AF:

0.00927

AC:

AN:

1294

South Asian (SAS)

AF:

0.00751

AC:

AN:

1198

European-Finnish (FIN)

AF:

0.00998

AC:

AN:

2604

Middle Eastern (MID)

AF:

0.0417

AC:

AN:

European-Non Finnish (NFE)

AF:

0.00606

AC:

137

AN:

22608

Other (OTH)

AF:

0.00530

AC:

AN:

566

⚠️ The allele balance in gnomAD version 4 Genomes is significantly skewed from the expected value of 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: 0.282

Heterozygous variant carriers

130

163

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:

0.0592

Hom.:

ClinVar

ClinVar submissions

Significance:Likely benign

Revision:criteria provided, multiple submitters, no conflicts

View on ClinVar

Pathogenic

VUS

Benign

Condition

not provided (2)

not specified (2)

FMN2-related disorder (1)

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.60

(source)

DANN

Benign

0.35

PhyloP100

-0.84

Mutation Taster

=100/0

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

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Publications

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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