dbSNP rs200503778: FMN2:p.Ala952Gly (chr1-240207667-C-G) – ACMG Classification: Benign (-12 pts)

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_StrongBP6_Very_Strong

The NM_020066.5(FMN2):c.2855C>G(p.Ala952Gly) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 14/20 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. A952A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0064 ( 1 hom., cov: 11)

Exomes 𝑓: 0.0063 ( 202 hom. )

Failed GnomAD Quality Control

Consequence

FMN2
NM_020066.5 missense

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: -3.13

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 links:

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -12 ACMG points.

BP4

Computational evidence support a benign effect (MetaRNN=0.005420178).

BP6

Variant 1-240207667-C-G is Benign according to our data. Variant chr1-240207667-C-G is described in ClinVar as [Likely_benign]. Clinvar id is 377218.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-240207667-C-G is described in Lovd as [Benign].

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN2	NM_020066.5 link	c.2855C>G	p.Ala952Gly	missense_variant	Exon 5 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.2855C>G	p.Ala952Gly	missense_variant	Exon 5 of 18	5	NM_020066.5	ENSP00000318884.9		Q9NZ56-1

Frequencies

GnomAD3 genomes

AF:

0.00644

AC:

372

AN:

57762

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00428

Gnomad AMI

AF:

0.00465

Gnomad AMR

AF:

0.00376

Gnomad ASJ

AF:

0.00504

Gnomad EAS

AF:

0.00231

Gnomad SAS

AF:

0.0230

Gnomad FIN

AF:

0.00620

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00753

Gnomad OTH

AF:

0.00264

GnomAD3 exomes

AF:

0.00524

AC:

1112

AN:

212370

Hom.:

AF XY:

0.00613

AC XY:

709

AN XY:

115750

show subpopulations

Gnomad AFR exome

AF:

0.00272

Gnomad AMR exome

AF:

0.00224

Gnomad ASJ exome

AF:

0.00223

Gnomad EAS exome

AF:

0.00208

Gnomad SAS exome

AF:

0.0192

Gnomad FIN exome

AF:

0.00380

Gnomad NFE exome

AF:

0.00387

Gnomad OTH exome

AF:

0.00434

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00632

AC:

7100

AN:

1123696

Hom.:

202

Cov.:

AF XY:

0.00708

AC XY:

3961

AN XY:

559778

show subpopulations

Gnomad4 AFR exome

AF:

0.00452

Gnomad4 AMR exome

AF:

0.00531

Gnomad4 ASJ exome

AF:

0.0146

Gnomad4 EAS exome

AF:

0.0140

Gnomad4 SAS exome

AF:

0.0213

Gnomad4 FIN exome

AF:

0.00791

Gnomad4 NFE exome

AF:

0.00460

Gnomad4 OTH exome

AF:

0.00894

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00643

AC:

372

AN:

57810

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

169

AN XY:

28226

show subpopulations

Gnomad4 AFR

AF:

0.00427

Gnomad4 AMR

AF:

0.00376

Gnomad4 ASJ

AF:

0.00504

Gnomad4 EAS

AF:

0.00231

Gnomad4 SAS

AF:

0.0229

Gnomad4 FIN

AF:

0.00620

Gnomad4 NFE

AF:

0.00753

Gnomad4 OTH

AF:

0.00262

Alfa

AF:

0.0176

Hom.:

ExAC

AF:

0.00439

AC:

528

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:3

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

Sep 20, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Nov 09, 2020

GeneDx

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

AlphaMissense

Benign

0.056

BayesDel_addAF

Benign

-0.62

BayesDel_noAF

Benign

-0.65

CADD

Benign

0.17

DANN

Benign

0.54

DEOGEN2

Benign

0.046

Eigen

Benign

-1.5

Eigen_PC

Benign

-1.5

FATHMM_MKL

Benign

0.00077

LIST_S2

Benign

0.42

MetaRNN

Benign

0.0054

MetaSVM

Benign

-1.0

MutationAssessor

Benign

-0.61

PrimateAI

Uncertain

0.66

PROVEAN

Benign

-0.69

REVEL

Benign

0.052

Sift

Benign

1.0

Sift4G

Benign

0.56

Polyphen

0.0

Vest4

0.074

MVP

0.56

MPC

0.092

ClinPred

0.0014

GERP RS

-2.0

Varity_R

0.030

gMVP

0.091

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

LitVar

Below is the list of publications found by LitVar. It may be empty.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over