Variant 1-12011376-C-G details in Genebe, Genetics Data Aggregator

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_StrongBP6_Very_StrongBA1

The NM_014874.4(MFN2):c.2205-120C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0759 in 1,046,330 control chromosomes in the GnomAD database, including 3,715 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

Frequency

Genomes: 𝑓 0.080 ( 591 hom., cov: 33)

Exomes 𝑓: 0.075 ( 3124 hom. )

Consequence

MFN2
NM_014874.4 intron

Scores

Clinical Significance

Benign criteria provided, multiple submitters, no conflicts B:2

Conservation

PhyloP100: -0.828

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 links:

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ACMG classification

Classification made for transcript

Verdict is Benign. Variant got -20 ACMG points.

BP4

Computational evidence support a benign effect (BayesDel_noAF=-0.9).

BP6

Variant 1-12011376-C-G is Benign according to our data. Variant chr1-12011376-C-G is described in ClinVar as [Benign]. Clinvar id is 1284248.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.

BA1

GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.138 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFN2	NM_014874.4 linkuse as main transcript	c.2205-120C>G		intron_variant		ENST00000235329.10	NP_055689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFN2	ENST00000235329.10 linkuse as main transcript	c.2205-120C>G		intron_variant		1	NM_014874.4	ENSP00000235329	P1	O95140-1

Frequencies

GnomAD3 genomes

AF:

0.0801

AC:

12187

AN:

152108

Hom.:

590

Cov.:

show subpopulations

Gnomad AFR

AF:

0.110

Gnomad AMI

AF:

0.0813

Gnomad AMR

AF:

0.0410

Gnomad ASJ

AF:

0.0352

Gnomad EAS

AF:

0.144

Gnomad SAS

AF:

0.148

Gnomad FIN

AF:

0.0750

Gnomad MID

AF:

0.0222

Gnomad NFE

AF:

0.0644

Gnomad OTH

AF:

0.0737

GnomAD4 exome

AF:

0.0752

AC:

67266

AN:

894104

Hom.:

3124

AF XY:

0.0774

AC XY:

35840

AN XY:

462984

show subpopulations

Gnomad4 AFR exome

AF:

0.106

Gnomad4 AMR exome

AF:

0.0345

Gnomad4 ASJ exome

AF:

0.0407

Gnomad4 EAS exome

AF:

0.152

Gnomad4 SAS exome

AF:

0.145

Gnomad4 FIN exome

AF:

0.0761

Gnomad4 NFE exome

AF:

0.0652

Gnomad4 OTH exome

AF:

0.0788

GnomAD4 genome

AF:

0.0801

AC:

12193

AN:

152226

Hom.:

591

Cov.:

AF XY:

0.0814

AC XY:

6061

AN XY:

74432

show subpopulations

Gnomad4 AFR

AF:

0.110

Gnomad4 AMR

AF:

0.0409

Gnomad4 ASJ

AF:

0.0352

Gnomad4 EAS

AF:

0.144

Gnomad4 SAS

AF:

0.147

Gnomad4 FIN

AF:

0.0750

Gnomad4 NFE

AF:

0.0644

Gnomad4 OTH

AF:

0.0734

Alfa

AF:

0.0277

Hom.:

Bravo

AF:

0.0754

Asia WGS

AF:

0.151

AC:

524

AN:

3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

LINK: link

Submissions by phenotype

not provided

Benign:2

Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -
Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 23, 2018	- -

Computational scores

Source: dbNSFP v4.3

Name

Calibrated prediction

Score

Prediction

BayesDel_noAF

Benign

-0.90

CADD

Benign

0.20

DANN

Benign

0.45

Splicing

Name

Calibrated prediction

Score

Prediction

SpliceAI score (max)

0.0

Details are displayed if max score is > 0.2

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