chr1-240092805-T-C
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Variant summary
Our verdict is Benign. Variant got -21 ACMG points: 0P and 21B. BP4_StrongBP6_Very_StrongBP7BS1BS2
The NM_020066.5(FMN2):āc.696T>Cā(p.Pro232=) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00457 in 1,585,654 control chromosomes in the GnomAD database, including 24 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (ā ā ).
Frequency
Genomes: š 0.0039 ( 1 hom., cov: 33)
Exomes š: 0.0046 ( 23 hom. )
Consequence
FMN2
NM_020066.5 synonymous
NM_020066.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.00300
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]
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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=-0.82).
BP6
Variant 1-240092805-T-C is Benign according to our data. Variant chr1-240092805-T-C is described in ClinVar as [Likely_benign]. Clinvar id is 435216.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
BP7
Synonymous conserved (PhyloP=-0.003 with no splicing effect.
BS1
Variant frequency is greater than expected in population nfe. gnomad4 allele frequency = 0.00387 (589/152240) while in subpopulation NFE AF= 0.00594 (404/67998). AF 95% confidence interval is 0.00546. There are 1 homozygotes in gnomad4. There are 278 alleles in male gnomad4 subpopulation. Median coverage is 33. This position pass quality control queck.
BS2
High Homozygotes in GnomAdExome4 at 23 AR gene
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FMN2 | NM_020066.5 | c.696T>C | p.Pro232= | synonymous_variant | 1/18 | ENST00000319653.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FMN2 | ENST00000319653.14 | c.696T>C | p.Pro232= | synonymous_variant | 1/18 | 5 | NM_020066.5 | P1 | |
FMN2 | ENST00000447095.5 | c.-87+24732T>C | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00387 AC: 589AN: 152122Hom.: 1 Cov.: 33
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GnomAD3 exomes AF: 0.00378 AC: 728AN: 192700Hom.: 3 AF XY: 0.00381 AC XY: 400AN XY: 105032
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GnomAD4 exome AF: 0.00465 AC: 6661AN: 1433414Hom.: 23 Cov.: 89 AF XY: 0.00451 AC XY: 3205AN XY: 710578
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GnomAD4 genome AF: 0.00387 AC: 589AN: 152240Hom.: 1 Cov.: 33 AF XY: 0.00373 AC XY: 278AN XY: 74438
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:4
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | Invitae | Dec 31, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Mar 01, 2024 | FMN2: BP4, BP7, BS2 - |
not specified Benign:1
Benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Nov 17, 2015 | - - |
FMN2-related disorder Benign:1
Benign, criteria provided, single submitter | clinical testing | PreventionGenetics, part of Exact Sciences | Jun 28, 2019 | This 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
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Name
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BayesDel_noAF
Benign
CADD
Benign
DANN
Benign
Splicing
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SpliceAI score (max)
Details are displayed if max score is > 0.2
Find out detailed SpliceAI scores and Pangolin per-transcript scores at