1-11981920-G-GTTTTTTTT

Position:

• chr1-11981920-G-GTTTTTTTT

Variant summary

Our verdict is Likely benign. Variant got -2 ACMG points: 0P and 2B. BP6_Moderate

The ENST00000235329.10(MFN2):​c.-149-45_-149-38dupTTTTTTTT variant causes a intron change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Benign (★). There are indicators that this mutation may affect the branch point..

• Frequency:
  • Genomes: 𝑓 0.16 (2429 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MFN2 ENST00000235329.10 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• 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]

MFN2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 1-11981920-G-GTTTTTTTT is Benign according to our data. Variant chr1-11981920-G-GTTTTTTTT is described in ClinVar as [Benign]. Clinvar id is 1243265.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFN2	NM_014874.4	c.-149-45_-149-38dupTTTTTTTT		intron_variant		ENST00000235329.10	NP_055689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFN2	ENST00000235329.10	c.-149-45_-149-38dupTTTTTTTT		intron_variant		1	NM_014874.4	ENSP00000235329.5

Frequencies

GnomAD3 genomes AF: 0.00 AC: 22310 AN: 137530 Hom.: 2428 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.235

Gnomad AMI AF: 0.136

Gnomad AMR AF: 0.103

Gnomad ASJ AF: 0.116

Gnomad EAS AF: 0.237

Gnomad SAS AF: 0.220

Gnomad FIN AF: 0.0754

Gnomad MID AF: 0.109

Gnomad NFE AF: 0.139

Gnomad OTH AF: 0.151

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: 0.162 AC: 22307 AN: 137534 Hom.: 2429 Cov.: 0 AF XY: 0.159 AC XY: 10507 AN XY: 66030

Gnomad4 AFR AF: 0.235

Gnomad4 AMR AF: 0.103

Gnomad4 ASJ AF: 0.116

Gnomad4 EAS AF: 0.237

Gnomad4 SAS AF: 0.220

Gnomad4 FIN AF: 0.0754

Gnomad4 NFE AF: 0.139

Gnomad4 OTH AF: 0.150

ClinVar

Significance: Benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Benign, criteria provided, single submitter

clinical testing

GeneDx

Oct 23, 2019

- -

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;