1-11980417-C-T

Variant summary

Our verdict is Likely benign. The variant received -2 ACMG points: 2P and 4B. PM2BP4_Strong

The ENST00000484391.5(MFN2):​n.48C>T variant causes a non coding transcript exon change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000406 in 246,056 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

Frequency

Genomes: not found (cov: 33)
Exomes 𝑓: 0.0000041 ( 0 hom. )

Consequence

MFN2
ENST00000484391.5 non_coding_transcript_exon

Scores

2

Clinical Significance

Not reported in ClinVar

Conservation

PhyloP100: -0.947

Publications

0 publications found
Variant links:
Genes affected
MFN2 (HGNC:16877): (mitofusin 2) This gene encodes a mitochondrial membrane protein that participates in mitochondrial fusion and contributes to the maintenance and operation of the mitochondrial network. This protein is involved in the regulation of vascular smooth muscle cell proliferation, and it may play a role in the pathophysiology of obesity. Mutations in this gene cause Charcot-Marie-Tooth disease type 2A2, and hereditary motor and sensory neuropathy VI, which are both disorders of the peripheral nervous system. Defects in this gene have also been associated with early-onset stroke. Two transcript variants encoding the same protein have been identified. [provided by RefSeq, Jul 2008]
MFN2 Gene-Disease associations (from GenCC):
  • neuropathy, hereditary motor and sensory, type 6A
    Inheritance: AD Classification: DEFINITIVE Submitted by: G2P
  • Charcot-Marie-Tooth disease, axonal, autosomal recessive, type 2a2b;
    Inheritance: AR Classification: DEFINITIVE, STRONG Submitted by: Labcorp Genetics (formerly Invitae), G2P
  • axonal hereditary motor and sensory neuropathy
    Inheritance: SD Classification: DEFINITIVE Submitted by: ClinGen
  • Charcot-Marie-Tooth disease type 2A2
    Inheritance: AD Classification: STRONG, SUPPORTIVE Submitted by: Orphanet, Labcorp Genetics (formerly Invitae)
  • hereditary motor and sensory neuropathy type 6
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • multiple symmetric lipomatosis
    Inheritance: AD Classification: SUPPORTIVE Submitted by: Orphanet
  • severe early-onset axonal neuropathy due to MFN2 deficiency
    Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet

Genome browser will be placed here

ACMG classification

Classification was made for transcript

Our verdict: Likely_benign. The variant received -2 ACMG points.

PM2
Very rare variant in population databases, with high coverage;
BP4
Computational evidence support a benign effect (BayesDel_noAF=-0.85).

Transcripts

RefSeq

Gene Transcript HGVSc HGVSp Effect Exon rank MANE Protein UniProt
MFN2NM_014874.4 linkc.-217C>T upstream_gene_variant ENST00000235329.10 NP_055689.1 O95140-1

Ensembl

Gene Transcript HGVSc HGVSp Effect Exon rank TSL MANE Protein Appris UniProt
MFN2ENST00000235329.10 linkc.-217C>T upstream_gene_variant 1 NM_014874.4 ENSP00000235329.5 O95140-1

Frequencies

GnomAD3 genomes
Cov.:
33
GnomAD4 exome
AF:
0.00000406
AC:
1
AN:
246056
Hom.:
0
Cov.:
0
AF XY:
0.00000802
AC XY:
1
AN XY:
124728
show subpopulations
African (AFR)
AF:
0.00
AC:
0
AN:
7162
American (AMR)
AF:
0.00
AC:
0
AN:
7426
Ashkenazi Jewish (ASJ)
AF:
0.00
AC:
0
AN:
9218
East Asian (EAS)
AF:
0.00
AC:
0
AN:
22888
South Asian (SAS)
AF:
0.00
AC:
0
AN:
3032
European-Finnish (FIN)
AF:
0.00
AC:
0
AN:
20826
Middle Eastern (MID)
AF:
0.00
AC:
0
AN:
1294
European-Non Finnish (NFE)
AF:
0.00000633
AC:
1
AN:
157860
Other (OTH)
AF:
0.00
AC:
0
AN:
16350
Allele Balance Distribution
Red line indicates average allele balance
Average allele balance: 0.425
Heterozygous variant carriers
0
0
1
1
2
2
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
Cov.:
33

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name
Calibrated prediction
Score
Prediction
BayesDel_noAF
Benign
-0.85
CADD
Benign
5.9
DANN
Benign
0.80
PhyloP100
-0.95
PromoterAI
0.0024
Neutral
RBP_binding_hub_radar
0.0
RBP_regulation_power_radar
1.1

Splicing

Name
Calibrated prediction
Score
Prediction
SpliceAI score (max)
0.010
Details are displayed if max score is > 0.2

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

Publications

Other links and lift over

dbSNP: rs886045218; hg19: chr1-12040474; API