Genetic Variant FMN2:c.4910+173T>C (chr1-240392735-T-C) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_StrongBA1

The NM_020066.5(FMN2):c.4910+173T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.548 in 152,030 control chromosomes in the GnomAD database, including 24,282 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: 𝑓 0.55 ( 24282 hom., cov: 33)

Consequence

FMN2
NM_020066.5 intron

Scores

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -2.07

Publications

2 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: Benign. The variant received -12 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.94).

BA1

GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.745 is higher than 0.05.

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	Effect	Exon Rank	Protein
FMN2	NM_020066.5	MANE Select	c.4910+173T>C	intron	N/A	NP_064450.3
FMN2	NM_001305424.2		c.4922+173T>C	intron	N/A	NP_001292353.1
FMN2	NM_001348094.2		c.2738+173T>C	intron	N/A	NP_001335023.1

Ensembl Transcripts

Gene	Transcript	Tags	HGVSc	Effect	Exon Rank	Protein	UniProt
FMN2	ENST00000319653.14	TSL:5 MANE Select	c.4910+173T>C	intron	N/A	ENSP00000318884.9	Q9NZ56-1
FMN2	ENST00000679980.1		c.1178+173T>C	intron	N/A	ENSP00000505449.1	A0A7P0T994
FMN2	ENST00000681210.1		c.1130+173T>C	intron	N/A	ENSP00000505131.1	A0A7P0Z432

Frequencies

GnomAD3 genomes

AF:

0.547

AC:

83132

AN:

151910

Hom.:

24225

Cov.:

show subpopulations

Gnomad AFR

AF:

0.752

Gnomad AMI

AF:

0.445

Gnomad AMR

AF:

0.560

Gnomad ASJ

AF:

0.476

Gnomad EAS

AF:

0.659

Gnomad SAS

AF:

0.491

Gnomad FIN

AF:

0.358

Gnomad MID

AF:

0.484

Gnomad NFE

AF:

0.451

Gnomad OTH

AF:

0.527

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome

AF:

0.548

AC:

83253

AN:

152030

Hom.:

24282

Cov.:

AF XY:

0.542

AC XY:

40272

AN XY:

74330

show subpopulations

African (AFR)

AF:

0.752

AC:

31202

AN:

41480

American (AMR)

AF:

0.560

AC:

8552

AN:

15276

Ashkenazi Jewish (ASJ)

AF:

0.476

AC:

1651

AN:

3466

East Asian (EAS)

AF:

0.659

AC:

3400

AN:

5160

South Asian (SAS)

AF:

0.491

AC:

2367

AN:

4820

European-Finnish (FIN)

AF:

0.358

AC:

3785

AN:

10570

Middle Eastern (MID)

AF:

0.476

AC:

139

AN:

292

European-Non Finnish (NFE)

AF:

0.451

AC:

30624

AN:

67948

Other (OTH)

AF:

0.535

AC:

1128

AN:

2108

Allele Balance Distribution

Red line indicates average allele balance

Average allele balance: 0.500

Heterozygous variant carriers

1774

3548

5321

7095

8869

0.00

0.20

0.40

0.60

0.80

0.95

Allele balance

Age Distribution

Genome Het

Genome Hom

Variant carriers

702

1404

2106

2808

3510

<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:

0.495

Hom.:

2358

Bravo

AF:

0.574

Asia WGS

AF:

0.611

AC:

2118

AN:

3476

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.94

CADD

Benign

0.19

(source)

DANN

Benign

0.60

PhyloP100

-2.1

Mutation Taster

=100/0

polymorphism (auto)

(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

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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

ClinVar

Computational scores

Splicing

Publications

Other links and lift over