1-240092766-ACAGCAGCAGCAG-ACAGCAGCAGCAGCAG

Variant summary

Our verdict is Benign. Variant got -16 ACMG points: 0P and 16B. BP6_Very_StrongBS1BS2

The NM_020066.5(FMN2):​c.674_676dup​(p.Gln225dup) variant causes a inframe insertion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00163 in 1,609,674 control chromosomes in the GnomAD database, including 37 homozygotes. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.0094 ( 19 hom., cov: 33)
Exomes 𝑓: 0.00082 ( 18 hom. )

Consequence

FMN2
NM_020066.5 inframe_insertion

Scores

Not classified

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.0480
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 -16 ACMG points.

BP6
Variant 1-240092766-A-ACAG is Benign according to our data. Variant chr1-240092766-A-ACAG is described in ClinVar as [Benign]. Clinvar id is 435215.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BS1
Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00936 (1424/152104) while in subpopulation AFR AF= 0.0321 (1333/41532). AF 95% confidence interval is 0.0307. There are 19 homozygotes in gnomad4. There are 692 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAd4 at 19 AR gene

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect #exon/exons MANE Protein UniProt
FMN2NM_020066.5 linkuse as main transcriptc.674_676dup p.Gln225dup inframe_insertion 1/18 ENST00000319653.14 NP_064450.3

Ensembl

Gene Transcript HGVSc HGVSp Effect #exon/exons TSL MANE Protein Appris UniProt
FMN2ENST00000319653.14 linkuse as main transcriptc.674_676dup p.Gln225dup inframe_insertion 1/185 NM_020066.5 ENSP00000318884 P1Q9NZ56-1
FMN2ENST00000447095.5 linkuse as main transcriptc.-87+24710_-87+24712dup intron_variant 3 ENSP00000409308

Frequencies

GnomAD3 genomes
AF:
0.00929
AC:
1412
AN:
151992
Hom.:
18
Cov.:
33
show subpopulations
Gnomad AFR
AF:
0.0319
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00412
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.000207
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.000147
Gnomad OTH
AF:
0.00813
GnomAD3 exomes
AF:
0.00187
AC:
417
AN:
223544
Hom.:
3
AF XY:
0.00151
AC XY:
184
AN XY:
121756
show subpopulations
Gnomad AFR exome
AF:
0.0249
Gnomad AMR exome
AF:
0.00173
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000595
Gnomad SAS exome
AF:
0.0000701
Gnomad FIN exome
AF:
0.00
Gnomad NFE exome
AF:
0.000122
Gnomad OTH exome
AF:
0.000720
GnomAD4 exome
AF:
0.000820
AC:
1195
AN:
1457570
Hom.:
18
Cov.:
88
AF XY:
0.000716
AC XY:
519
AN XY:
724938
show subpopulations
Gnomad4 AFR exome
AF:
0.0275
Gnomad4 AMR exome
AF:
0.00179
Gnomad4 ASJ exome
AF:
0.00
Gnomad4 EAS exome
AF:
0.000101
Gnomad4 SAS exome
AF:
0.0000582
Gnomad4 FIN exome
AF:
0.00
Gnomad4 NFE exome
AF:
0.0000702
Gnomad4 OTH exome
AF:
0.00176
GnomAD4 genome
AF:
0.00936
AC:
1424
AN:
152104
Hom.:
19
Cov.:
33
AF XY:
0.00930
AC XY:
692
AN XY:
74372
show subpopulations
Gnomad4 AFR
AF:
0.0321
Gnomad4 AMR
AF:
0.00412
Gnomad4 ASJ
AF:
0.00
Gnomad4 EAS
AF:
0.00
Gnomad4 SAS
AF:
0.000207
Gnomad4 FIN
AF:
0.00
Gnomad4 NFE
AF:
0.000147
Gnomad4 OTH
AF:
0.00805
Bravo
AF:
0.00992

ClinVar

Significance: Benign
Submissions summary: Benign:2
Revision: criteria provided, multiple submitters, no conflicts
LINK: link

Submissions by phenotype

not specified Benign:1
Benign, criteria provided, single submitterclinical testingGenetic Services Laboratory, University of ChicagoDec 30, 2016- -
not provided Benign:1
Benign, criteria provided, single submitterclinical testingLabcorp Genetics (formerly Invitae), LabcorpAug 17, 2019- -

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction

Splicing

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: rs532298569; hg19: chr1-240256066; API