1-11999355-C-T

Position:

• chr1-11999355-C-T

Variant summary

Our verdict is Benign. Variant got -14 ACMG points: 0P and 14B. BP4_Strong BP6_Moderate BA1

The NM_014874.4(MFN2):​c.816+260C>T variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.46 in 151,936 control chromosomes in the GnomAD database, including 17,069 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.46 (17069 hom., cov: 31)
• Consequence: MFN2 NM_014874.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 0.0300

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 -14 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.8).
• BP6: Variant 1-11999355-C-T is Benign according to our data. Variant chr1-11999355-C-T is described in ClinVar as [Benign]. Clinvar id is 684255.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (NFE) allele frequency at 95% confidence interval = 0.526 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFN2	NM_014874.4	c.816+260C>T		intron_variant		ENST00000235329.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFN2	ENST00000235329.10	c.816+260C>T		intron_variant		1	NM_014874.4	P1

Frequencies

GnomAD3 genomes AF: 0.460 AC: 69870 AN: 151818 Hom.: 17069 Cov.: 31

Gnomad AFR AF: 0.320

Gnomad AMI AF: 0.335

Gnomad AMR AF: 0.447

Gnomad ASJ AF: 0.375

Gnomad EAS AF: 0.409

Gnomad SAS AF: 0.466

Gnomad FIN AF: 0.632

Gnomad MID AF: 0.500

Gnomad NFE AF: 0.531

Gnomad OTH AF: 0.466

We have no GnomAD4 exomes data on this position. Probably position not covered by the project.

GnomAD4 genome AF: 0.460 AC: 69901 AN: 151936 Hom.: 17069 Cov.: 31 AF XY: 0.462 AC XY: 34324 AN XY: 74270

Gnomad4 AFR AF: 0.320

Gnomad4 AMR AF: 0.447

Gnomad4 ASJ AF: 0.375

Gnomad4 EAS AF: 0.410

Gnomad4 SAS AF: 0.467

Gnomad4 FIN AF: 0.632

Gnomad4 NFE AF: 0.531

Gnomad4 OTH AF: 0.467

Alfa AF: 0.514 Hom.: 41865

Bravo AF: 0.442

Asia WGS AF: 0.435 AC: 1513 AN: 3478

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

Jun 19, 2018

This variant is considered likely benign or benign based on one or more of the following criteria: it is a conservative change, it occurs at a poorly conserved position in the protein, it is predicted to be benign by multiple in silico algorithms, and/or has population frequency not consistent with disease. -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.80
CADD	Benign	5.8
DANN	Benign	0.74

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.0		Details are displayed if max score is > 0.2

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

Publications

LitVar

Other links and lift over

dbSNP: rs2295281; hg19: chr1-12059412;