rs873457

chr1-11986277-C-G

Variant summary

Our verdict is Benign. Variant got -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_014874.4(MFN2):c.-4-2888C>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.623 in 152,052 control chromosomes in the GnomAD database, including 29,877 homozygotes. 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: 𝑓 0.62 (29877 hom., cov: 32)
• Consequence: MFN2 NM_014874.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -2.35

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]

ACMG classification

Verdict is Benign. Variant got -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.91).
• BA1: GnomAd4 highest subpopulation (SAS) allele frequency at 95% confidence interval = 0.663 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFN2	NM_014874.4	c.-4-2888C>G		intron_variant		ENST00000235329.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFN2	ENST00000235329.10	c.-4-2888C>G		intron_variant		1	NM_014874.4	P1

Frequencies

GnomAD3 genomes AF: 0.623 AC: 94680 AN: 151934 Hom.: 29867 Cov.: 32

Gnomad AFR AF: 0.596

Gnomad AMI AF: 0.476

Gnomad AMR AF: 0.533

Gnomad ASJ AF: 0.484

Gnomad EAS AF: 0.637

Gnomad SAS AF: 0.681

Gnomad FIN AF: 0.736

Gnomad MID AF: 0.589

Gnomad NFE AF: 0.647

Gnomad OTH AF: 0.608

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.623 AC: 94733 AN: 152052 Hom.: 29877 Cov.: 32 AF XY: 0.625 AC XY: 46451 AN XY: 74314

Gnomad4 AFR AF: 0.596

Gnomad4 AMR AF: 0.533

Gnomad4 ASJ AF: 0.484

Gnomad4 EAS AF: 0.638

Gnomad4 SAS AF: 0.682

Gnomad4 FIN AF: 0.736

Gnomad4 NFE AF: 0.647

Gnomad4 OTH AF: 0.607

Alfa AF: 0.631 Hom.: 3805

Bravo AF: 0.603

Asia WGS AF: 0.661 AC: 2298 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.91
Cadd	Benign	0.48
Dann	Benign	0.45

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

LitVar

Other links and lift over

dbSNP: rs873457; hg19: chr1-12046334;