rs188083977

chr1-240207635-A-Cchr1-240207635-A-Gchr1-240207635-A-T

Variant summary

Our verdict is Benign. Variant got -13 ACMG points: 0P and 13B. BP4_Strong BP6_Very_Strong BP7

The NM_020066.5(FMN2):c.2823A>C(p.Gly941=) 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
• Clinical Significance: Likely benign criteria provided, multiple submitters, no conflicts B:3
• Conservation: PhyloP100: -0.845

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]

ACMG classification

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/exons	MANE	UniProt
FMN2	NM_020066.5	c.2823A>C	p.Gly941=	synonymous_variant	5/18	ENST00000319653.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN2	ENST00000319653.14	c.2823A>C	p.Gly941=	synonymous_variant	5/18	5	NM_020066.5	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 312 AN: 42832 Hom.: 0 Cov.: 0 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.: 0 AF XY: 0.000504 AC XY: 58 AN XY: 115120

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.: 12 Cov.: 36 AF XY: 0.000961 AC XY: 407 AN XY: 423356

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.: 0 Cov.: 0 AF XY: 0.00747 AC XY: 154 AN XY: 20626

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.: 0

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not specified Benign:1

Likely benign, criteria provided, single submitter

clinical testing

Genetic Services Laboratory, University of Chicago

Sep 18, 2015

- -

not provided Benign:1

Likely benign, criteria provided, single submitter

clinical testing

CeGaT Center for Human Genetics Tuebingen

Nov 01, 2022

FMN2: BP4, BP7 -

FMN2-related disorder Benign:1

Likely benign, criteria provided, single submitter

clinical testing

PreventionGenetics, part of Exact Sciences

Jun 21, 2019

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

Other links and lift over

dbSNP: rs188083977; hg19: chr1-240370935; COSMIC: COSV60419915; COSMIC: COSV60419915;