dbSNP rs188083977: FMN2:p.Gly941Gly (chr1-240207635-A-C) – ACMG Classification: Benign (-13 pts)

Variant summary

Our verdict is Benign. Variant got -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:4

Conservation

PhyloP100: -0.845

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 -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 id 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.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN2	NM_020066.5 link	c.2823A>C	p.Gly941Gly	synonymous_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.2823A>C	p.Gly941Gly	synonymous_variant	Exon 5 of 18	5	NM_020066.5	ENSP00000318884.9		Q9NZ56-1

Frequencies

GnomAD3 genomes

AF:

0.00

AC:

312

AN:

42832

Hom.:

Cov.:

FAILED QC

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

GnomAD3 exomes

AF:

0.000548

AC:

116

AN:

211838

Hom.:

AF XY:

0.000504

AC XY:

AN XY:

115120

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 SAS exome

AF:

0.000463

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

Gnomad4 AFR exome

AF:

0.00102

Gnomad4 AMR exome

AF:

0.00137

Gnomad4 ASJ exome

AF:

0.00170

Gnomad4 EAS exome

AF:

0.00180

Gnomad4 SAS exome

AF:

0.00213

Gnomad4 FIN exome

AF:

0.00118

Gnomad4 NFE exome

AF:

0.000844

Gnomad4 OTH exome

AF:

0.00166

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

Gnomad4 AFR

AF:

0.00939

Gnomad4 AMR

AF:

0.00633

Gnomad4 ASJ

AF:

0.00643

Gnomad4 EAS

AF:

0.00927

Gnomad4 SAS

AF:

0.00751

Gnomad4 FIN

AF:

0.00998

Gnomad4 NFE

AF:

0.00606

Gnomad4 OTH

AF:

0.00530

Alfa

AF:

0.0592

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Nov 01, 2022

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FMN2: BP4, BP7 -

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

not specified

Benign:1

Sep 18, 2015

Genetic Services Laboratory, University of Chicago

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

FMN2-related disorder

Benign:1

Jun 21, 2019

PreventionGenetics, part of Exact Sciences

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

This variant is classified as likely benign based on ACMG/AMP sequence variant interpretation guidelines (Richards et al. 2015 PMID: 25741868, with internal and published modifications). -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.91

CADD

Benign

0.60

DANN

Benign

0.35

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