1-11982204-A-G

Position:

• chr1-11982204-A-G

Variant summary

Our verdict is Benign. Variant got -20 ACMG points: 0P and 20B. BP4_Strong BP6_Very_Strong BA1

The ENST00000235329.10(MFN2):​c.-5+90A>G variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.571 in 151,990 control chromosomes in the GnomAD database, including 26,561 homozygotes. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency:
  • Genomes: 𝑓 0.57 (26561 hom., cov: 32)
  • Exomes 𝑓: 0.25 (1 hom.)
  • Failed GnomAD Quality Control
• Consequence: MFN2 ENST00000235329.10 intron
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2
• Conservation: PhyloP100: 1.78

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 -20 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.7).
• BP6: Variant 1-11982204-A-G is Benign according to our data. Variant chr1-11982204-A-G is described in ClinVar as [Benign]. Clinvar id is 1279097.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.776 is higher than 0.05.

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt
MFN2	NM_014874.4	c.-5+90A>G		intron_variant		ENST00000235329.10	NP_055689.1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MFN2	ENST00000235329.10	c.-5+90A>G		intron_variant		1	NM_014874.4	ENSP00000235329	P1

Frequencies

GnomAD3 genomes AF: 0.571 AC: 86744 AN: 151872 Hom.: 26525 Cov.: 32

Gnomad AFR AF: 0.783

Gnomad AMI AF: 0.246

Gnomad AMR AF: 0.463

Gnomad ASJ AF: 0.330

Gnomad EAS AF: 0.679

Gnomad SAS AF: 0.610

Gnomad FIN AF: 0.594

Gnomad MID AF: 0.440

Gnomad NFE AF: 0.470

Gnomad OTH AF: 0.533

GnomAD4 exome Data not reliable, filtered out with message: AS_VQSR AF: 0.250 AC: 4 AN: 16 Hom.: 1 AF XY: 0.333 AC XY: 4 AN XY: 12

Gnomad4 FIN exome AF: 0.00

Gnomad4 NFE exome AF: 0.200

Gnomad4 OTH exome AF: 0.500

GnomAD4 genome AF: 0.571 AC: 86845 AN: 151990 Hom.: 26561 Cov.: 32 AF XY: 0.574 AC XY: 42637 AN XY: 74280

Gnomad4 AFR AF: 0.783

Gnomad4 AMR AF: 0.463

Gnomad4 ASJ AF: 0.330

Gnomad4 EAS AF: 0.680

Gnomad4 SAS AF: 0.609

Gnomad4 FIN AF: 0.594

Gnomad4 NFE AF: 0.470

Gnomad4 OTH AF: 0.535

Alfa AF: 0.542 Hom.: 5076

Bravo AF: 0.567

Asia WGS AF: 0.670 AC: 2329 AN: 3478

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

not provided Benign:2

Benign, criteria provided, single submitter	clinical testing	GeneDx	Jun 29, 2018	- -
Benign, criteria provided, single submitter	not provided	Breakthrough Genomics, Breakthrough Genomics	-	- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.70
CADD	Benign	15
DANN	Benign	0.86

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: rs2236055; hg19: chr1-12042261;