1-240092640-G-A

Variant summary

Our verdict is Benign. Variant got -19 ACMG points: 0P and 19B. BP4_ModerateBP6_Very_StrongBP7BS1BS2

The NM_020066.5(FMN2):​c.531G>A​(p.Ser177=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.000631 in 1,614,104 control chromosomes in the GnomAD database, including 5 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★★).

Frequency

Genomes: 𝑓 0.0028 ( 2 hom., cov: 33)
Exomes 𝑓: 0.00040 ( 3 hom. )

Consequence

FMN2
NM_020066.5 synonymous

Scores

2

Clinical Significance

Benign/Likely benign criteria provided, multiple submitters, no conflicts B:5

Conservation

PhyloP100: -0.405
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]

Genome browser will be placed here

ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -19 ACMG points.

BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.4).
BP6
Variant 1-240092640-G-A is Benign according to our data. Variant chr1-240092640-G-A is described in ClinVar as [Likely_benign]. Clinvar id is 435214.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars. Variant chr1-240092640-G-A is described in Lovd as [Likely_benign].
BP7
Synonymous conserved (PhyloP=-0.405 with no splicing effect.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.0028 (426/152298) while in subpopulation AFR AF= 0.0095 (395/41568). AF 95% confidence interval is 0.00873. There are 2 homozygotes in gnomad4. There are 185 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 2 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE UniProt
FMN2NM_020066.5 linkuse as main transcriptc.531G>A p.Ser177= synonymous_variant 1/18 ENST00000319653.14

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Appris UniProt
FMN2ENST00000319653.14 linkuse as main transcriptc.531G>A p.Ser177= synonymous_variant 1/185 NM_020066.5 P1Q9NZ56-1
FMN2ENST00000447095.5 linkuse as main transcriptc.-87+24567G>A intron_variant 3

Frequencies

GnomAD3 genomes
AF:
0.00278
AC:
423
AN:
152180
Hom.:
2
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.00946
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.000654
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.000471
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000162
Gnomad OTH
AF:
0.00239
GnomAD3 exomes
AF:
0.000846
AC:
211
AN:
249262
Hom.:
2
AF XY:
0.000719
AC XY:
97
AN XY:
134966
show subpopulations
Gnomad AFR exome
AF:
0.00936
Gnomad AMR exome
AF:
0.000492
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.00
Gnomad SAS exome
AF:
0.000555
Gnomad FIN exome
AF:
0.000185
Gnomad NFE exome
AF:
0.000161
Gnomad OTH exome
AF:
0.000490
GnomAD4 exome
AF:
0.000405
AC:
592
AN:
1461806
Hom.:
3
Cov.:
89
AF XY:
0.000393
AC XY:
286
AN XY:
727216
show subpopulations
Gnomad4 AFR exome
AF:
0.0102
Gnomad4 AMR exome
AF:
0.000537
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.00
Gnomad4 SAS exome
AF:
0.000661
Gnomad4 FIN exome
AF:
0.000225
Gnomad4 NFE exome
AF:
0.0000989
Gnomad4 OTH exome
AF:
0.000811
GnomAD4 genome
AF:
0.00280
AC:
426
AN:
152298
Hom.:
2
Cov.:
33
AF XY:
0.00248
AC XY:
185
AN XY:
74464
show subpopulations
Gnomad4 AFR
AF:
0.00950
Gnomad4 AMR
AF:
0.000653
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.00
Gnomad4 FIN
AF:
0.000471
Gnomad4 NFE
AF:
0.000162
Gnomad4 OTH
AF:
0.00237
Alfa
AF:
0.000640
Hom.:
2
Bravo
AF:
0.00312
Asia WGS
AF:
0.000866
AC:
3
AN:
3478
EpiCase
AF:
0.000436
EpiControl
AF:
0.000237

ClinVar

Significance: Benign/Likely benign
Submissions summary: Benign:5
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not provided Benign:3
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpDec 31, 2019- -
Likely benign, criteria provided, single submitterclinical testingCeGaT Center for Human Genetics TuebingenDec 01, 2023FMN2: BP4, BP7, BS2 -
Likely benign, criteria provided, single submitternot providedBreakthrough Genomics, Breakthrough Genomics-- -
not specified Benign:1
Likely benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoMar 31, 2017- -
FMN2-related disorder Benign:1
Benign, no assertion criteria providedclinical testingPreventionGenetics, part of Exact SciencesOct 14, 2019This variant is classified as 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
-0.40
CADD
Benign
8.9
DANN
Benign
0.95

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.

Other links and lift over

dbSNP: rs148480631; hg19: chr1-240255940; API