rs1474868

chr1-11984107-C-T

Variant summary

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

The NM_014874.4(MFN2):c.-5+1993C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.533 in 152,036 control chromosomes in the GnomAD database, including 22,521 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 0.53 (22521 hom., cov: 33)
• Consequence: MFN2 NM_014874.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -1.05

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=-0.86).
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.662 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFN2	NM_014874.4	c.-5+1993C>T		intron_variant		ENST00000235329.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFN2	ENST00000235329.10	c.-5+1993C>T		intron_variant		1	NM_014874.4	P1

Frequencies

GnomAD3 genomes AF: 0.533 AC: 81023 AN: 151918 Hom.: 22499 Cov.: 33

Gnomad AFR AF: 0.655

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.444

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.680

Gnomad SAS AF: 0.608

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.389

Gnomad NFE AF: 0.469

Gnomad OTH AF: 0.499

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

GnomAD4 genome AF: 0.533 AC: 81102 AN: 152036 Hom.: 22521 Cov.: 33 AF XY: 0.538 AC XY: 39978 AN XY: 74296

Gnomad4 AFR AF: 0.655

Gnomad4 AMR AF: 0.444

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.681

Gnomad4 SAS AF: 0.608

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.469

Gnomad4 OTH AF: 0.501

Alfa AF: 0.491 Hom.: 13252

Bravo AF: 0.523

Asia WGS AF: 0.662 AC: 2299 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.86
Cadd	Benign	0.42
Dann	Benign	0.49

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

Other links and lift over

dbSNP: rs1474868; hg19: chr1-12044164;