1-240207698-A-G

Variant names:

Variant summary

Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2

The NM_020066.5(FMN2):c.2886A>G(p.Ala962Ala) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0113 in 756,088 control chromosomes in the GnomAD database, including 189 homozygotes. In-silico tool predicts 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. A962A) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0057 ( 0 hom., cov: 0)

Exomes 𝑓: 0.012 ( 189 hom. )

Consequence

FMN2
NM_020066.5 synonymous

Scores

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:4

Conservation

PhyloP100: -2.99

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 -21 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.92).

BP6

Variant 1-240207698-A-G is Benign according to our data. Variant chr1-240207698-A-G is described in ClinVar as [Likely_benign]. Clinvar id is 435228.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BP7

Synonymous conserved (PhyloP=-2.99 with no splicing effect.

BS1

Variant frequency is greater than expected in population sas. gnomad4 allele frequency = 0.00572 (278/48592) while in subpopulation SAS AF= 0.0073 (10/1370). AF 95% confidence interval is 0.00609. There are 0 homozygotes in gnomad4. There are 137 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.

BS2

High Homozygotes in GnomAdExome4 at 189 AR gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
FMN2	NM_020066.5 link	c.2886A>G	p.Ala962Ala	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.2886A>G	p.Ala962Ala	synonymous_variant	Exon 5 of 18	5	NM_020066.5	ENSP00000318884.9		Q9NZ56-1

Frequencies

GnomAD3 genomes

AF:

0.00573

AC:

278

AN:

48554

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.00369

Gnomad AMI

AF:

0.00245

Gnomad AMR

AF:

0.00489

Gnomad ASJ

AF:

0.00160

Gnomad EAS

AF:

0.00327

Gnomad SAS

AF:

0.00733

Gnomad FIN

AF:

0.00847

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00692

Gnomad OTH

AF:

0.00

GnomAD4 exome

AF:

0.0117

AC:

8256

AN:

707496

Hom.:

189

Cov.:

AF XY:

0.0121

AC XY:

4282

AN XY:

354284

show subpopulations

Gnomad4 AFR exome

AF:

0.00855

Gnomad4 AMR exome

AF:

0.00764

Gnomad4 ASJ exome

AF:

0.0349

Gnomad4 EAS exome

AF:

0.0391

Gnomad4 SAS exome

AF:

0.0111

Gnomad4 FIN exome

AF:

0.0120

Gnomad4 NFE exome

AF:

0.0103

Gnomad4 OTH exome

AF:

0.0189

GnomAD4 genome

AF:

0.00572

AC:

278

AN:

48592

Hom.:

Cov.:

AF XY:

0.00599

AC XY:

137

AN XY:

22876

show subpopulations

Gnomad4 AFR

AF:

0.00368

Gnomad4 AMR

AF:

0.00488

Gnomad4 ASJ

AF:

0.00160

Gnomad4 EAS

AF:

0.00326

Gnomad4 SAS

AF:

0.00730

Gnomad4 FIN

AF:

0.00847

Gnomad4 NFE

AF:

0.00692

Gnomad4 OTH

AF:

0.00

Alfa

AF:

0.0812

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:4

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

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

- -

not provided

Benign:1

Breakthrough Genomics, Breakthrough Genomics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: not provided

- -

FMN2-related disorder

Benign:1

Oct 24, 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). -

Intellectual disability, autosomal recessive 47

Benign:1

Oct 30, 2023

Revvity Omics, Revvity

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.92

CADD

Benign

2.5

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