1-11981920-GTTT-GTTTTTTTTTTTTT

Variant names:

• chr1-11981920-G-GTTTTTTTTTT
• rs34602102
• NM_014874.4:c.-149-47_-149-38dupTTTTTTTTTT

Variant summary

Our verdict is Benign. Variant got -8 ACMG points: 0P and 8B. BS1 BS2

The NM_014874.4(MFN2):​c.-149-47_-149-38dupTTTTTTTTTT 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 0.0013 (2 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 Benign. Variant got -8 ACMG points.

• BS1: Variant frequency is greater than expected in population afr. gnomad4 allele frequency = 0.00126 (174/137990) while in subpopulation AFR AF= 0.00469 (167/35594). AF 95% confidence interval is 0.00411. There are 2 homozygotes in gnomad4. There are 82 alleles in male gnomad4 subpopulation. Median coverage is 0. This position pass quality control queck.
• BS2: High Homozygotes in GnomAd4 at 2 SD gene

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
MFN2	NM_014874.4	c.-149-47_-149-38dupTTTTTTTTTT		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.-149-47_-149-38dupTTTTTTTTTT		intron_variant	Intron 1 of 18	1	NM_014874.4	ENSP00000235329.5

Frequencies

GnomAD3 genomes AF: 0.00124 AC: 171 AN: 137984 Hom.: 2 Cov.: 0

Gnomad AFR AF: 0.00461

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0000712

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.000212

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.0000459

Gnomad OTH AF: 0.00106

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

GnomAD4 genome AF: 0.00126 AC: 174 AN: 137990 Hom.: 2 Cov.: 0 AF XY: 0.00124 AC XY: 82 AN XY: 66258

Gnomad4 AFR AF: 0.00469

Gnomad4 AMR AF: 0.0000711

Gnomad4 ASJ AF: 0.00

Gnomad4 EAS AF: 0.000212

Gnomad4 SAS AF: 0.00

Gnomad4 FIN AF: 0.00

Gnomad4 NFE AF: 0.0000459

Gnomad4 OTH AF: 0.00106

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;