1-11981920-G-GTTTTTTT

Position:

• chr1-11981920-G-GTTTTTTT

Variant summary

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

The NM_014874.4(MFN2):​c.-149-44_-149-38dup 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 0.33 (8014 hom., cov: 0)
  • Failed GnomAD Quality Control
• Consequence: MFN2 NM_014874.4 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]

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 1-11981920-G-GTTTTTTT is Benign according to our data. Variant chr1-11981920-G-GTTTTTTT is described in ClinVar as [Benign]. Clinvar id is 1238604.Status of the report is criteria_provided_single_submitter, 1 stars.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFN2	NM_014874.4	c.-149-44_-149-38dup		intron_variant		ENST00000235329.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFN2	ENST00000235329.10	c.-149-44_-149-38dup		intron_variant		1	NM_014874.4	P1

Frequencies

GnomAD3 genomes AF: 0.00 AC: 44737 AN: 137284 Hom.: 8015 Cov.: 0 FAILED QC

Gnomad AFR AF: 0.347

Gnomad AMI AF: 0.0907

Gnomad AMR AF: 0.311

Gnomad ASJ AF: 0.204

Gnomad EAS AF: 0.412

Gnomad SAS AF: 0.371

Gnomad FIN AF: 0.416

Gnomad MID AF: 0.299

Gnomad NFE AF: 0.308

Gnomad OTH AF: 0.315

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: 0.326 AC: 44738 AN: 137288 Hom.: 8014 Cov.: 0 AF XY: 0.328 AC XY: 21594 AN XY: 65856

Gnomad4 AFR AF: 0.347

Gnomad4 AMR AF: 0.312

Gnomad4 ASJ AF: 0.204

Gnomad4 EAS AF: 0.412

Gnomad4 SAS AF: 0.370

Gnomad4 FIN AF: 0.416

Gnomad4 NFE AF: 0.308

Gnomad4 OTH AF: 0.314

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;