rs758726356
Variant summary
Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4BP6_Very_StrongBS1
The NM_020066.5(FMN2):βc.2844_2876delβ(p.Ala952_Ala962del) variant causes a inframe deletion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (β β ).
Frequency
Genomes: π 0.0077 ( 0 hom., cov: 0)
Exomes π: 0.0045 ( 32 hom. )
Failed GnomAD Quality Control
Consequence
FMN2
NM_020066.5 inframe_deletion
NM_020066.5 inframe_deletion
Scores
Not classified
Clinical Significance
Conservation
PhyloP100: 2.82
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 -10 ACMG points.
PM4
?
Nonframeshift variant in NON repetitive region in NM_020066.5.
BP6
?
Variant 1-240207641-TCCTCCGCCCCCTCTACCCGGAGCGGCAATACCC-T is Benign according to our data. Variant chr1-240207641-TCCTCCGCCCCCTCTACCCGGAGCGGCAATACCC-T is described in ClinVar as [Likely_benign]. Clinvar id is 446013.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 = 0.00774 (358/46266) while in subpopulation AFR AF= 0.0154 (146/9494). AF 95% confidence interval is 0.0133. There are 0 homozygotes in gnomad4. There are 160 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
Transcripts
RefSeq
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | MANE | UniProt |
---|---|---|---|---|---|---|---|
FMN2 | NM_020066.5 | c.2844_2876del | p.Ala952_Ala962del | inframe_deletion | 5/18 | ENST00000319653.14 |
Ensembl
Gene | Transcript | HGVSc | HGVSp | Effect | #exon/exons | TSL | MANE | Appris | UniProt |
---|---|---|---|---|---|---|---|---|---|
FMN2 | ENST00000319653.14 | c.2844_2876del | p.Ala952_Ala962del | inframe_deletion | 5/18 | 5 | NM_020066.5 | P1 |
Frequencies
GnomAD3 genomes ? AF: 0.00774 AC: 358AN: 46244Hom.: 0 Cov.: 0
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GnomAD3 exomes AF: 0.00242 AC: 530AN: 219330Hom.: 1 AF XY: 0.00235 AC XY: 279AN XY: 118972
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GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.00445 AC: 3844AN: 863656Hom.: 32 AF XY: 0.00430 AC XY: 1833AN XY: 426264
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ClinVar
Significance: Benign/Likely benign
Submissions summary: Benign:3
Revision: criteria provided, multiple submitters, no conflicts
LINK: link
Submissions by phenotype
not provided Benign:2
Benign, criteria provided, single submitter | clinical testing | CeGaT Center for Human Genetics Tuebingen | Jul 01, 2024 | FMN2: BS1, BS2 - |
Likely benign, criteria provided, single submitter | clinical testing | Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics | Apr 27, 2017 | - - |
not specified Benign:1
Likely benign, criteria provided, single submitter | clinical testing | Women's Health and Genetics/Laboratory Corporation of America, LabCorp | Mar 06, 2024 | Variant summary: FMN2 c.2844_2876del33 (p.Ala952_Ala962del) results in an in-frame deletion that is predicted to remove 11 amino acids from Formin, FH2 domain (IPR015425) of the encoded protein. This variant is within a repeat region, consist of GIPLPPPLPGA or GIPPPPPLPGA, and inframe del/dup from this region have not been reported in HGMD. The variant allele was found at a frequency of 0.0024 in 219330 control chromosomes in the gnomAD database, including 1 homozygotes. To our knowledge, no occurrence of c.2844_2876del33 in individuals affected with Intellectual Disability, Autosomal Recessive 47 and no experimental evidence demonstrating its impact on protein function have been reported. ClinVar contains an entry for this variant (Variation ID: 446013). Based on the evidence outlined above, the variant was classified as likely benign. - |
Computational scores
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Find out detailed SpliceAI scores and Pangolin per-transcript scores at