rs2605141

Variant names:

• chr17-18260925-T-C
• rs2605141
• NM_139162.4:c.-8+188T>C

Variant summary

Our verdict is Benign. The variant received -12 ACMG points: 0P and 12B. BP4_Strong BA1

The NM_139162.4(MIEF2):​c.-8+188T>C variant causes a intron change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.718 in 152,108 control chromosomes in the GnomAD database, including 39,916 homozygotes. In-silico tool predicts a benign outcome for this variant. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Genomes: 𝑓 0.72 (39916 hom., cov: 33)
• Consequence: MIEF2 NM_139162.4 intron
• Clinical Significance: Not reported in ClinVar
• Conservation: PhyloP100: -0.295
• Publications: 9 publications found

Genes affected

MIEF2 (HGNC:17920): (mitochondrial elongation factor 2) This gene encodes an outer mitochondrial membrane protein that functions in the regulation of mitochondrial morphology. It can directly recruit the fission mediator dynamin-related protein 1 (Drp1) to the mitochondrial surface. The gene is located within the Smith-Magenis syndrome region on chromosome 17. Alternative splicing results in multiple transcript variants encoding different isoforms. [provided by RefSeq, Jun 2011]

MIEF2 Gene-Disease associations (from GenCC):

• combined oxidative phosphorylation deficiency 49

  Inheritance: Unknown Classification: LIMITED Submitted by: Labcorp Genetics (formerly Invitae)

ACMG classification

Our verdict: Benign. The variant received -12 ACMG points.

• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.87).
• BA1: GnomAd4 highest subpopulation (AFR) allele frequency at 95% confidence interval = 0.85 is higher than 0.05.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_139162.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIEF2	NM_139162.4	MANE Select	c.-8+188T>C		intron	N/A	NP_631901.2
	MIEF2	NM_001144900.3		c.-8+188T>C		intron	N/A	NP_001138372.1	Q96C03-2
	MIEF2	NM_148886.2		c.-211T>C		upstream_gene	N/A	NP_683684.2	Q96C03-3

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MIEF2	ENST00000323019.9	TSL:2 MANE Select	c.-8+188T>C		intron	N/A	ENSP00000323591.4	Q96C03-1
	MIEF2	ENST00000902907.1		c.-136+188T>C		intron	N/A	ENSP00000572966.1
	MIEF2	ENST00000902908.1		c.-4+188T>C		intron	N/A	ENSP00000572967.1

Frequencies

GnomAD3 genomes AF: 0.718 AC: 109103 AN: 151990 Hom.: 39868 Cov.: 33

Gnomad AFR AF: 0.857

Gnomad AMI AF: 0.556

Gnomad AMR AF: 0.691

Gnomad ASJ AF: 0.698

Gnomad EAS AF: 0.544

Gnomad SAS AF: 0.563

Gnomad FIN AF: 0.697

Gnomad MID AF: 0.661

Gnomad NFE AF: 0.670

Gnomad OTH AF: 0.703

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

GnomAD4 genome AF: 0.718 AC: 109217 AN: 152108 Hom.: 39916 Cov.: 33 AF XY: 0.714 AC XY: 53107 AN XY: 74348

African (AFR) AF: 0.857 AC: 35600 AN: 41532

American (AMR) AF: 0.691 AC: 10571 AN: 15290

Ashkenazi Jewish (ASJ) AF: 0.698 AC: 2422 AN: 3472

East Asian (EAS) AF: 0.544 AC: 2798 AN: 5140

South Asian (SAS) AF: 0.564 AC: 2719 AN: 4824

European-Finnish (FIN) AF: 0.697 AC: 7380 AN: 10590

Middle Eastern (MID) AF: 0.646 AC: 190 AN: 294

European-Non Finnish (NFE) AF: 0.670 AC: 45549 AN: 67944

Other (OTH) AF: 0.702 AC: 1482 AN: 2112

Alfa AF: 0.717 Hom.: 5885

Bravo AF: 0.722

Asia WGS AF: 0.543 AC: 1891 AN: 3478

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.87
CADD	Benign	7.2
DANN	Benign	0.57
PhyloP100		-0.29
PromoterAI		-0.046	Neutral
Mutation Taster		=100/0	polymorphism (auto)

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

Other links and lift over

dbSNP: rs2605141; hg19: chr17-18164239;