1-240092640-G-A
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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
NM_020066.5 synonymous
Scores
2
Clinical Significance
Conservation
PhyloP100: -0.405
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 -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 |
---|---|---|---|---|---|---|---|
FMN2 | NM_020066.5 | c.531G>A | p.Ser177= | synonymous_variant | 1/18 | ENST00000319653.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FMN2 | ENST00000319653.14 | c.531G>A | p.Ser177= | synonymous_variant | 1/18 | 5 | NM_020066.5 | P1 | |
FMN2 | ENST00000447095.5 | c.-87+24567G>A | intron_variant | 3 |
Frequencies
GnomAD3 genomes AF: 0.00278 AC: 423AN: 152180Hom.: 2 Cov.: 33
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GnomAD3 exomes AF: 0.000846 AC: 211AN: 249262Hom.: 2 AF XY: 0.000719 AC XY: 97AN XY: 134966
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GnomAD4 exome AF: 0.000405 AC: 592AN: 1461806Hom.: 3 Cov.: 89 AF XY: 0.000393 AC XY: 286AN XY: 727216
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GnomAD4 genome AF: 0.00280 AC: 426AN: 152298Hom.: 2 Cov.: 33 AF XY: 0.00248 AC XY: 185AN XY: 74464
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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 submitter | clinical testing | Labcorp Genetics (formerly Invitae), Labcorp | Dec 31, 2019 | - - |
Likely benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Dec 01, 2023 | FMN2: BP4, BP7, BS2 - |
Likely benign, criteria provided, single submitter | not provided | Breakthrough Genomics, Breakthrough Genomics | - | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Genetic Services Laboratory, University of Chicago | Mar 31, 2017 | - - |
FMN2-related disorder Benign:1
Benign, no assertion criteria provided | clinical testing | PreventionGenetics, part of Exact Sciences | Oct 14, 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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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