GeneBe

chr1-240092268-GGGCGGC-G

Variant names:

Variant summary

Our verdict is Uncertain significance. The variant received 1 ACMG points: 2P and 1B. PM2BP3

The NM_020066.5(FMN2):​c.171_176delCGGCGG​(p.Gly58_Gly59del) variant causes a disruptive inframe deletion change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0000155 in 1,415,034 control chromosomes in the GnomAD database, with no homozygous occurrence. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. Synonymous variant affecting the same amino acid position (i.e. G57G) has been classified as Likely benign.

Frequency

Genomes: 𝑓 0.0 ( 0 hom., cov: 0)
Exomes 𝑓: 0.000016 ( 0 hom. )
Failed GnomAD Quality Control

Consequence

FMN2
NM_020066.5 disruptive_inframe_deletion

Scores

Not classified

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: 2.10

Publications

6 publications found
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 Gene-Disease associations (from GenCC):
  • intellectual disability, autosomal recessive 47
    Inheritance: AR Classification: STRONG Submitted by: Labcorp Genetics (formerly Invitae), Ambry Genetics, G2P
  • autosomal recessive non-syndromic intellectual disability
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Uncertain_significance. The variant received 1 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP3
Nonframeshift variant in repetitive region in NM_020066.5

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_020066.5. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
FMN2
NM_020066.5
MANE Select
c.171_176delCGGCGGp.Gly58_Gly59del
disruptive_inframe_deletion
Exon 1 of 18NP_064450.3
FMN2
NM_001305424.2
c.171_176delCGGCGGp.Gly58_Gly59del
disruptive_inframe_deletion
Exon 1 of 19NP_001292353.1
FMN2
NM_001348094.2
c.171_176delCGGCGGp.Gly58_Gly59del
disruptive_inframe_deletion
Exon 1 of 15NP_001335023.1

Ensembl Transcripts

Sel.
GeneTranscriptTagsHGVScHGVSpEffectExon RankProteinUniProt
FMN2
ENST00000319653.14
TSL:5 MANE Select
c.171_176delCGGCGGp.Gly58_Gly59del
disruptive_inframe_deletion
Exon 1 of 18ENSP00000318884.9Q9NZ56-1
FMN2
ENST00000447095.5
TSL:3
c.-87+24207_-87+24212delCGGCGG
intron
N/AENSP00000409308.1B0QZA8

Frequencies

GnomAD3 genomes
AF:
0.00
AC:
0
AN:
149534
Hom.:
0
Cov.:
0
Gnomad AFR
AF:
0.00
Gnomad AMI
AF:
0.00
Gnomad AMR
AF:
0.00
Gnomad ASJ
AF:
0.00
Gnomad EAS
AF:
0.00
Gnomad SAS
AF:
0.00
Gnomad FIN
AF:
0.00
Gnomad MID
AF:
0.00
Gnomad NFE
AF:
0.00
Gnomad OTH
AF:
0.00
GnomAD2 exomes
AF:
0.000114
AC:
20
AN:
175182
AF XY:
0.0000837
show subpopulations
Gnomad AFR exome
AF:
0.000323
Gnomad AMR exome
AF:
0.0000728
Gnomad ASJ exome
AF:
0.00
Gnomad EAS exome
AF:
0.0000705
Gnomad FIN exome
AF:
0.0000644
Gnomad NFE exome
AF:
0.000181
Gnomad OTH exome
AF:
0.00
GnomAD4 exome
AF:
0.0000155
AC:
22
AN:
1415034
Hom.:
0
AF XY:
0.0000143
AC XY:
10
AN XY:
699604
show subpopulations
⚠️ The allele balance in gnomAD version 4 Exomes is significantly skewed from the expected value of 0.5.
African (AFR)
AF:
0.0000918
AC:
3
AN:
32686
American (AMR)
AF:
0.00
AC:
0
AN:
38920
Ashkenazi Jewish (ASJ)
AF:
0.0000403
AC:
1
AN:
24834
East Asian (EAS)
AF:
0.00
AC:
0
AN:
38418
South Asian (SAS)
AF:
0.00
AC:
0
AN:
80434
European-Finnish (FIN)
AF:
0.0000418
AC:
2
AN:
47870
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
5046
European-Non Finnish (NFE)
AF:
0.0000138
AC:
15
AN:
1088326
Other (OTH)
AF:
0.0000171
AC:
1
AN:
58500
⚠️ The allele balance in gnomAD4 Exomes is highly skewed from 0.5 (p-value = 0), which strongly suggests a high chance of mosaicism in these individuals.
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.261
Heterozygous variant carriers
0
3
6
10
13
16
0.00
0.20
0.40
0.60
0.80
0.95
Allele balance

Age Distribution

Exome Het
Variant carriers
0
2
4
6
8
10
<30
30-35
35-40
40-45
45-50
50-55
55-60
60-65
65-70
70-75
75-80
>80
Age
GnomAD4 genome
Data not reliable, filtered out with message: AC0
AF:
0.00
AC:
0
AN:
149534
Hom.:
0
Cov.:
0
AF XY:
0.00
AC XY:
0
AN XY:
72804
African (AFR)
AF:
0.00
AC:
0
AN:
40558
American (AMR)
AF:
0.00
AC:
0
AN:
15096
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
3438
East Asian (EAS)
AF:
0.00
AC:
0
AN:
4970
South Asian (SAS)
AF:
0.00
AC:
0
AN:
4720
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
10160
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
314
European-Non Finnish (NFE)
AF:
0.00
AC:
0
AN:
67328
Other (OTH)
AF:
0.00
AC:
0
AN:
2054
Alfa
AF:
0.00119
Hom.:
4337

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name
Calibrated prediction
Score
Prediction
PhyloP100
2.1
Mutation Taster
=168/32
polymorphism

Splicing

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Publications

Other links and lift over

dbSNP: rs71929261; hg19: chr1-240255568; API