Variant chr1-240092268-GGGC-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 0P and 10B. BP6_ModerateBA1

The NM_020066.5(FMN2):c.174_176del(p.Gly59del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.764 in 1,415,582 control chromosomes in the GnomAD database, including 415,921 homozygotes. Variant has been reported in ClinVar as Benign (★). Synonymous variant affecting the same amino acid position (i.e. G54G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.77 ( 44723 hom., cov: 0)

Exomes 𝑓: 0.76 ( 415921 hom. )

Failed GnomAD Quality Control

Consequence

FMN2
NM_020066.5 inframe_deletion

Scores

Not classified

Clinical Significance

Benign criteria provided, single submitter B:1

Conservation

PhyloP100: 2.03

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:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -10 ACMG points.

BP6

Variant 1-240092268-GGGC-G is Benign according to our data. Variant chr1-240092268-GGGC-G is described in ClinVar as [Benign]. Clinvar id is 1285272.Status of the report is criteria_provided_single_submitter, 1 stars.

BA1

GnomAdExome4 highest subpopulation (AMR) allele frequency at 95% confidence interval = 0.775 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
FMN2	NM_020066.5 linkuse as main transcript	c.174_176del	p.Gly59del	inframe_deletion	1/18	ENST00000319653.14

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
FMN2	ENST00000319653.14 linkuse as main transcript	c.174_176del	p.Gly59del	inframe_deletion	1/18	5	NM_020066.5	P1	Q9NZ56-1
FMN2	ENST00000447095.5 linkuse as main transcript	c.-87+24210_-87+24212del		intron_variant		3

Frequencies

GnomAD3 genomes

AF:

0.770

AC:

115118

AN:

149410

Hom.:

44653

Cov.:

show subpopulations

Gnomad AFR

AF:

0.789

Gnomad AMI

AF:

0.748

Gnomad AMR

AF:

0.771

Gnomad ASJ

AF:

0.760

Gnomad EAS

AF:

0.453

Gnomad SAS

AF:

0.748

Gnomad FIN

AF:

0.830

Gnomad MID

AF:

0.688

Gnomad NFE

AF:

0.777

Gnomad OTH

AF:

0.762

GnomAD3 exomes

AF:

0.748

AC:

131017

AN:

175182

Hom.:

49969

AF XY:

0.748

AC XY:

71524

AN XY:

95582

show subpopulations

Gnomad AFR exome

AF:

0.783

Gnomad AMR exome

AF:

0.791

Gnomad ASJ exome

AF:

0.768

Gnomad EAS exome

AF:

0.437

Gnomad SAS exome

AF:

0.748

Gnomad FIN exome

AF:

0.832

Gnomad NFE exome

AF:

0.766

Gnomad OTH exome

AF:

0.769

GnomAD4 exome

AF:

0.764

AC:

1081365

AN:

1415582

Hom.:

415921

AF XY:

0.763

AC XY:

533724

AN XY:

699880

show subpopulations

Gnomad4 AFR exome

AF:

0.780

Gnomad4 AMR exome

AF:

0.782

Gnomad4 ASJ exome

AF:

0.761

Gnomad4 EAS exome

AF:

0.466

Gnomad4 SAS exome

AF:

0.744

Gnomad4 FIN exome

AF:

0.830

Gnomad4 NFE exome

AF:

0.772

Gnomad4 OTH exome

AF:

0.756

GnomAD4 genome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.771

AC:

115256

AN:

149522

Hom.:

44723

Cov.:

AF XY:

0.771

AC XY:

56162

AN XY:

72850

show subpopulations

Gnomad4 AFR

AF:

0.789

Gnomad4 AMR

AF:

0.771

Gnomad4 ASJ

AF:

0.760

Gnomad4 EAS

AF:

0.455

Gnomad4 SAS

AF:

0.750

Gnomad4 FIN

AF:

0.830

Gnomad4 NFE

AF:

0.777

Gnomad4 OTH

AF:

0.763

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

LINK: link

Submissions by phenotype

Intellectual disability, autosomal recessive 47

Benign:1

Benign, criteria provided, single submitter

clinical testing

Genome-Nilou Lab

Aug 10, 2021

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

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