rs878853115

Variant names:

• chrM-5302-T-C
• rs878853115
• ENST00000361453.3:c.833T>C

Variant summary

Our verdict is Benign. The variant received -13 ACMG points: 0P and 13B. BP4 BP6_Very_Strong BS2

The ENST00000361453.3(MT-ND2):​c.833T>C​(p.Ile278Thr) 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. I278V) has been classified as Benign.

• Frequency: Mitomap GenBank: 𝑓 0.00090 (AC: 52)
• Consequence: MT-ND2 ENST00000361453.3 missense
• Scores: Apogee2 Benign 0.048
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.257
• Publications: 8 publications found

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]

TRNW (HGNC:7501): (mitochondrially encoded tRNA tryptophan)

TRNW Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: DEFINITIVE Submitted by: ClinGen
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -13 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.047591355 < 0.5 .
• BP6: Variant M-5302-T-C is Benign according to our data. Variant chrM-5302-T-C is described in ClinVar as Benign. ClinVar VariationId is 235811.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BS2: High AC in GnomadMitoHomoplasmic at 52

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND2	unassigned_transcript_4793	c.833T>C	p.Ile278Thr	missense_variant	Exon 1 of 1
TRNW	unassigned_transcript_4794	c.-210T>C		upstream_gene_variant

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND2	ENST00000361453.3	c.833T>C	p.Ile278Thr	missense_variant	Exon 1 of 1	6		ENSP00000355046.4
MT-TW	ENST00000387382.1	n.-210T>C		upstream_gene_variant		6

Frequencies

Mitomap GenBank AF: 0.00090 AC: 52

Gnomad homoplasmic AF: 0.00092 AC: 52 AN: 56415

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56415

Alfa AF: 0.00156 Hom.: 6

Mitomap

No disease associated.

ClinVar

Significance: Benign

Submissions summary: Benign:2

Revision: criteria provided, multiple submitters, no conflicts

Submissions by phenotype

Leigh syndrome Benign:1

Oct 17, 2019

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

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

The NC_012920.1:m.5302T>C (YP_003024027.1:p.Ile278Thr) 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, BP4 -

not provided Benign:1

Jan 06, 2016

Center for Pediatric Genomic Medicine, Children's Mercy Hospital and Clinics

Significance: Benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

- -

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.048
Hmtvar	Benign	0.090
AlphaMissense	Uncertain	0.40
BayesDel_addAF	Benign	-0.56	T
DEOGEN2	Benign	0.065	T
LIST_S2	Benign	0.59	T
MutationAssessor	Benign	0.39	N
PhyloP100		0.26
PROVEAN	Uncertain	-2.5	D
Sift4G	Benign	0.43	T
GERP RS		3.0
Varity_R		0.11
Mutation Taster		=100/0	polymorphism

Other links and lift over

dbSNP: rs878853115; hg19: chrM-5303;