1-11981920-G-GTTTTTT

Position:

• chr1-11981920-G-GTTTTTT

Variant summary

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

The NM_014874.4(MFN2):​c.-149-43_-149-38dupTTTTTT 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 0.026 (204 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]

MFN2 (HGNC:):

ACMG classification

Verdict is Likely_benign. Variant got -2 ACMG points.

• BP6: Variant 1-11981920-G-GTTTTTT is Benign according to our data. Variant chr1-11981920-G-GTTTTTT is described in ClinVar as [Benign]. Clinvar id is 1251375.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.-149-43_-149-38dupTTTTTT		intron_variant		ENST00000235329.10	NP_055689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFN2	ENST00000235329.10	c.-149-43_-149-38dupTTTTTT		intron_variant		1	NM_014874.4	ENSP00000235329.5

Frequencies

GnomAD3 genomes AF: 0.0259 AC: 3570 AN: 137958 Hom.: 202 Cov.: 0

Gnomad AFR AF: 0.0840

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.0102

Gnomad ASJ AF: 0.000296

Gnomad EAS AF: 0.00127

Gnomad SAS AF: 0.00157

Gnomad FIN AF: 0.00762

Gnomad MID AF: 0.00352

Gnomad NFE AF: 0.00504

Gnomad OTH AF: 0.0218

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: 0.0259 AC: 3577 AN: 137964 Hom.: 204 Cov.: 0 AF XY: 0.0263 AC XY: 1740 AN XY: 66250

Gnomad4 AFR AF: 0.0841

Gnomad4 AMR AF: 0.0102

Gnomad4 ASJ AF: 0.000296

Gnomad4 EAS AF: 0.00127

Gnomad4 SAS AF: 0.00158

Gnomad4 FIN AF: 0.00762

Gnomad4 NFE AF: 0.00504

Gnomad4 OTH AF: 0.0216

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

Feb 21, 2020

- -

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;