rs387906426

Positions:

• chrM-4640-C-A

Variant summary

Our verdict is Benign. Variant got -7 ACMG points: 0P and 7B. BP4 BP6_Moderate BS2

The ENST00000361453.3(MT-ND2):​c.171C>A​(p.Ile57Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★). Another variant affecting the same amino acid position, but resulting in a different missense (i.e. I57T) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.0039 (AC: 240)
• Consequence: MT-ND2 ENST00000361453.3 missense
• Scores: Apogee2 Benign 0.083
• Clinical Significance: Benign criteria provided, single submitter P:1 B:1 O:1 LHON-/-Epilepsy
• Conservation: PhyloP100: -9.19

Genes affected

MT-ND2 (HGNC:7456): (mitochondrially encoded NADH dehydrogenase 2) Enables NADH dehydrogenase (ubiquinone) activity. Involved in mitochondrial electron transport, NADH to ubiquinone and mitochondrial respiratory chain complex I assembly. Part of mitochondrial respiratory chain complex I. Implicated in Leber hereditary optic neuropathy; multiple sclerosis; myocardial infarction; neurodegenerative disease (multiple); and urinary bladder cancer. [provided by Alliance of Genome Resources, Apr 2022]

ACMG classification

Verdict is Benign. Variant got -7 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.08323591 < 0.5 .
• BP6: Variant M-4640-C-A is Benign according to our data. Variant chrM-4640-C-A is described in ClinVar as [Benign]. Clinvar id is 9718.Status of the report is criteria_provided_single_submitter, 1 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 66

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	MANE	Protein	UniProt

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	#exon/exons	TSL	MANE	Protein	Appris	UniProt
MT-ND2	ENST00000361453.3	c.171C>A	p.Ile57Met	missense_variant	1/1			ENSP00000355046	P1

Frequencies

GnomAD4 exome Cov.: 0

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

Mitomap GenBank AF: 0.0039 AC: 240

Gnomad homoplasmic AF: 0.0012 AC: 66 AN: 56434

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56434

Alfa AF: 0.00506 Hom.: 22

Mitomap

LHON-/-Epilepsy

ClinVar

Significance: Benign

Submissions summary: Pathogenic:1 Benign:1 Other:1

Revision: criteria provided, single submitter

Submissions by phenotype

Leber optic atrophy Pathogenic:1 Other:1

not provided, no classification provided	literature only	GeneReviews	-	- -
Pathogenic, no assertion criteria provided	literature only	OMIM	Jul 01, 2001	- -

Leigh syndrome Benign:1

Benign, criteria provided, single submitter

clinical testing

Wong Mito Lab, Molecular and Human Genetics, Baylor College of Medicine

Oct 17, 2019

The NC_012920.1:m.4640C>A (YP_003024027.1:p.Ile57Met) variant in MTND2 gene is interpretated to be a Benign variant based on the modified ACMG guidelines (unpublished). This variant meets the following evidence codes: BS1, BS2 -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.083
Hmtvar	Pathogenic	0.70
AlphaMissense	Benign	0.16

Splicing

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

Publications

LitVar

Other links and lift over

dbSNP: rs387906426; hg19: chrM-4641;