rs758726356

Variant names:

Variant summary

Our verdict is Benign. Variant got -10 ACMG points: 2P and 12B. PM4BP6_Very_StrongBS1

The NM_020066.5(FMN2):c.2844_2876delACCCGGAGCGGCAATACCCCCTCCGCCCCCTCT(p.Pro949_Leu959del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★★). Synonymous variant affecting the same amino acid position (i.e. L948L) has been classified as Benign.

Frequency

Genomes: 𝑓 0.0077 ( 0 hom., cov: 0)

Exomes 𝑓: 0.0045 ( 32 hom. )

Failed GnomAD Quality Control

Consequence

FMN2
NM_020066.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Likely benign criteria provided, multiple submitters, no conflicts B:3

Conservation

PhyloP100: 2.82

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]

FMN2 links:

Genome browser will be placed here

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 rank	MANE	Protein	UniProt
FMN2	NM_020066.5 link	c.2844_2876delACCCGGAGCGGCAATACCCCCTCCGCCCCCTCT	p.Pro949_Leu959del	disruptive_inframe_deletion	Exon 5 of 18	ENST00000319653.14	NP_064450.3	Q9NZ56-1Q9HBL1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
FMN2	ENST00000319653.14 link	c.2844_2876delACCCGGAGCGGCAATACCCCCTCCGCCCCCTCT	p.Pro949_Leu959del	disruptive_inframe_deletion	Exon 5 of 18	5	NM_020066.5	ENSP00000318884.9		Q9NZ56-1

Frequencies

GnomAD3 genomes

AF:

0.00774

AC:

358

AN:

46244

Hom.:

Cov.:

show subpopulations

Gnomad AFR

AF:

0.0154

Gnomad AMI

AF:

0.0510

Gnomad AMR

AF:

0.0107

Gnomad ASJ

AF:

0.00

Gnomad EAS

AF:

0.00

Gnomad SAS

AF:

0.00

Gnomad FIN

AF:

0.000312

Gnomad MID

AF:

0.00

Gnomad NFE

AF:

0.00576

Gnomad OTH

AF:

0.0100

GnomAD3 exomes

AF:

0.00242

AC:

530

AN:

219330

Hom.:

AF XY:

0.00235

AC XY:

279

AN XY:

118972

show subpopulations

Gnomad AFR exome

AF:

0.00535

Gnomad AMR exome

AF:

0.00344

Gnomad ASJ exome

AF:

0.000120

Gnomad EAS exome

AF:

0.000253

Gnomad SAS exome

AF:

0.000408

Gnomad FIN exome

AF:

0.000206

Gnomad NFE exome

AF:

0.00305

Gnomad OTH exome

AF:

0.00559

GnomAD4 exome

Data not reliable, filtered out with message: AS_VQSR

AF:

0.00445

AC:

3844

AN:

863656

Hom.:

AF XY:

0.00430

AC XY:

1833

AN XY:

426264

show subpopulations

Gnomad4 AFR exome

AF:

0.00843

Gnomad4 AMR exome

AF:

0.00505

Gnomad4 ASJ exome

AF:

0.000646

Gnomad4 EAS exome

AF:

0.000422

Gnomad4 SAS exome

AF:

0.000536

Gnomad4 FIN exome

AF:

0.000309

Gnomad4 NFE exome

AF:

0.00499

Gnomad4 OTH exome

AF:

0.00434

GnomAD4 genome

AF:

0.00774

AC:

358

AN:

46266

Hom.:

Cov.:

AF XY:

0.00726

AC XY:

160

AN XY:

22044

show subpopulations

Gnomad4 AFR

AF:

0.0154

Gnomad4 AMR

AF:

0.0107

Gnomad4 ASJ

AF:

0.00

Gnomad4 EAS

AF:

0.00

Gnomad4 SAS

AF:

0.00

Gnomad4 FIN

AF:

0.000312

Gnomad4 NFE

AF:

0.00576

Gnomad4 OTH

AF:

0.0100

Alfa

AF:

0.000506

Hom.:

ClinVar

Significance: Likely benign

Submissions summary: Benign:3

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Feb 01, 2025

CeGaT Center for Human Genetics Tuebingen

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

FMN2: PM4, BS1 -

Apr 27, 2017

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

not specified

Benign:1

Mar 06, 2024

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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

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.

Variant summary

Frequency

Consequence

Scores

Clinical Significance

Conservation

ACMG classification

Transcripts

RefSeq

Ensembl

Frequencies

ClinVar

Submissions by phenotype

Computational scores

Splicing

Publications

LitVar

Other links and lift over