1-11981920-GTTT-GTTTTTTTTTTTT

Variant names:

• chr1-11981920-G-GTTTTTTTTT
• rs34602102
• NM_014874.4:c.-149-46_-149-38dupTTTTTTTTT

Variant summary

Our verdict is Uncertain significance. Variant got 0 ACMG points: 0P and 0B.

The NM_014874.4(MFN2):​c.-149-46_-149-38dupTTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar. There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.027 (297 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MFN2 NM_014874.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: 0.194

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 Uncertain_significance. Variant got 0 ACMG points.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFN2	NM_014874.4	c.-149-46_-149-38dupTTTTTTTTT		intron_variant	Intron 1 of 18	ENST00000235329.10	NP_055689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MFN2	ENST00000235329.10	c.-149-46_-149-38dupTTTTTTTTT		intron_variant	Intron 1 of 18	1	NM_014874.4	ENSP00000235329.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 3788 AN: 137906 Hom.: 298 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.0965

Gnomad AMI AF: 0.00566

Gnomad AMR AF: 0.0117

Gnomad ASJ AF: 0.00178

Gnomad EAS AF: 0.00191

Gnomad SAS AF: 0.00404

Gnomad FIN AF: 0.000134

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.00185

Gnomad OTH AF: 0.0202

GnomAD4 exome Data not reliable, filtered out with message: AC0;AS_VQSR AC: 0 AN: 0 Hom.: 0 Cov.: 0 AC XY: 0 AN XY: 0

GnomAD4 genome Data not reliable, filtered out with message: AS_VQSR AF: 0.0275 AC: 3788 AN: 137912 Hom.: 297 Cov.: 0 AF XY: 0.0266 AC XY: 1764 AN XY: 66222

Gnomad4 AFR AF: 0.0964

Gnomad4 AMR AF: 0.0116

Gnomad4 ASJ AF: 0.00178

Gnomad4 EAS AF: 0.00191

Gnomad4 SAS AF: 0.00383

Gnomad4 FIN AF: 0.000134

Gnomad4 NFE AF: 0.00185

Gnomad4 OTH AF: 0.0201

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BranchPoint Hunter		3.0

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs34602102; hg19: chr1-12041977;