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
NM_020066.5 inframe_insertion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: -0.0480
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 |
---|---|---|---|---|---|---|---|---|
FMN2 | NM_020066.5 | c.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 |
---|---|---|---|---|---|---|---|---|---|---|
FMN2 | ENST00000319653.14 | c.674_676dup | p.Gln225dup | inframe_insertion | 1/18 | 5 | NM_020066.5 | ENSP00000318884 | P1 | |
FMN2 | ENST00000447095.5 | c.-87+24710_-87+24712dup | intron_variant | 3 | ENSP00000409308 |
Frequencies
GnomAD3 genomes AF: 0.00929 AC: 1412AN: 151992Hom.: 18 Cov.: 33
GnomAD3 genomes
AF:
AC:
1412
AN:
151992
Hom.:
Cov.:
33
Gnomad AFR
AF:
Gnomad AMI
AF:
Gnomad AMR
AF:
Gnomad ASJ
AF:
Gnomad EAS
AF:
Gnomad SAS
AF:
Gnomad FIN
AF:
Gnomad MID
AF:
Gnomad NFE
AF:
Gnomad OTH
AF:
GnomAD3 exomes AF: 0.00187 AC: 417AN: 223544Hom.: 3 AF XY: 0.00151 AC XY: 184AN XY: 121756
GnomAD3 exomes
AF:
AC:
417
AN:
223544
Hom.:
AF XY:
AC XY:
184
AN XY:
121756
Gnomad AFR exome
AF:
Gnomad AMR exome
AF:
Gnomad ASJ exome
AF:
Gnomad EAS exome
AF:
Gnomad SAS exome
AF:
Gnomad FIN exome
AF:
Gnomad NFE exome
AF:
Gnomad OTH exome
AF:
GnomAD4 exome AF: 0.000820 AC: 1195AN: 1457570Hom.: 18 Cov.: 88 AF XY: 0.000716 AC XY: 519AN XY: 724938
GnomAD4 exome
AF:
AC:
1195
AN:
1457570
Hom.:
Cov.:
88
AF XY:
AC XY:
519
AN XY:
724938
Gnomad4 AFR exome
AF:
Gnomad4 AMR exome
AF:
Gnomad4 ASJ exome
AF:
Gnomad4 EAS exome
AF:
Gnomad4 SAS exome
AF:
Gnomad4 FIN exome
AF:
Gnomad4 NFE exome
AF:
Gnomad4 OTH exome
AF:
GnomAD4 genome AF: 0.00936 AC: 1424AN: 152104Hom.: 19 Cov.: 33 AF XY: 0.00930 AC XY: 692AN XY: 74372
GnomAD4 genome
AF:
AC:
1424
AN:
152104
Hom.:
Cov.:
33
AF XY:
AC XY:
692
AN XY:
74372
Gnomad4 AFR
AF:
Gnomad4 AMR
AF:
Gnomad4 ASJ
AF:
Gnomad4 EAS
AF:
Gnomad4 SAS
AF:
Gnomad4 FIN
AF:
Gnomad4 NFE
AF:
Gnomad4 OTH
AF:
Bravo
AF:
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 submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Dec 30, 2016 | - - |
not provided Benign:1
Benign, criteria provided, single submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Aug 17, 2019 | - - |
Computational scores
Source:
Name
Calibrated prediction
Score
Prediction
Splicing
Find out detailed SpliceAI scores and Pangolin per-transcript scores at