rs3766742

chr1-12005113-A-G

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.1495+186A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.0472 in 152,150 control chromosomes in the GnomAD database, including 241 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★).

• Frequency: Genomes: 𝑓 0.047 (241 hom., cov: 33)
• Consequence: MFN2 NM_014874.4 intron
• Clinical Significance: Benign criteria provided, single submitter B:1
• Conservation: PhyloP100: -0.0450

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=-0.83).
• BP6: Variant 1-12005113-A-G is Benign according to our data. Variant chr1-12005113-A-G is described in ClinVar as [Benign]. Clinvar id is 1233343.Status of the report is criteria_provided_single_submitter, 1 stars.
• BA1: GnomAd4 highest subpopulation (EAS) allele frequency at 95% confidence interval = 0.119 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	UniProt
MFN2	NM_014874.4	c.1495+186A>G		intron_variant		ENST00000235329.10

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Appris	UniProt
MFN2	ENST00000235329.10	c.1495+186A>G		intron_variant		1	NM_014874.4	P1

Frequencies

GnomAD3 genomes AF: 0.0472 AC: 7171 AN: 152032 Hom.: 240 Cov.: 33

Gnomad AFR AF: 0.0234

Gnomad AMI AF: 0.0647

Gnomad AMR AF: 0.0422

Gnomad ASJ AF: 0.0857

Gnomad EAS AF: 0.126

Gnomad SAS AF: 0.0751

Gnomad FIN AF: 0.0178

Gnomad MID AF: 0.0633

Gnomad NFE AF: 0.0571

Gnomad OTH AF: 0.0465

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

GnomAD4 genome AF: 0.0472 AC: 7182 AN: 152150 Hom.: 241 Cov.: 33 AF XY: 0.0474 AC XY: 3529 AN XY: 74392

Gnomad4 AFR AF: 0.0235

Gnomad4 AMR AF: 0.0421

Gnomad4 ASJ AF: 0.0857

Gnomad4 EAS AF: 0.127

Gnomad4 SAS AF: 0.0756

Gnomad4 FIN AF: 0.0178

Gnomad4 NFE AF: 0.0571

Gnomad4 OTH AF: 0.0484

Alfa AF: 0.0467 Hom.: 33

Bravo AF: 0.0473

Asia WGS AF: 0.100 AC: 347 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 26, 2018

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.83
Cadd	Benign	7.6
Dann	Benign	0.40

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.020		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: rs3766742; hg19: chr1-12065170;