rs878853062

Variant names:

• chrM-4823-T-C
• rs878853062
• ENST00000361453.3:c.354T>C

Variant summary

Our verdict is Benign. The variant received -7 ACMG points: 0P and 7B. BP6_Moderate BP7 BS2

The ENST00000361453.3(MT-ND2):​c.354T>C​(p.Val118Val) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. Variant has been reported in ClinVar as Likely benign (★).

• Frequency: Mitomap GenBank: 𝑓 0.0048 (AC: 292)
• Consequence: MT-ND2 ENST00000361453.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: -15.7
• Publications: 3 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]

MT-ND2 Gene-Disease associations (from GenCC):

• mitochondrial disease

  Inheritance: Mitochondrial Classification: MODERATE Submitted by: ClinGen
• mitochondrial complex I deficiency

  Inheritance: AR Classification: SUPPORTIVE Submitted by: Orphanet
• Leber hereditary optic neuropathy

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• maternally-inherited Leigh syndrome

  Inheritance: Mitochondrial Classification: SUPPORTIVE Submitted by: Orphanet
• Leigh syndrome

  Inheritance: Mitochondrial Classification: LIMITED Submitted by: ClinGen

ACMG classification

Our verdict: Benign. The variant received -7 ACMG points.

• BP6: Variant M-4823-T-C is Benign according to our data. Variant chrM-4823-T-C is described in ClinVar as Likely_benign. ClinVar VariationId is 235544.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=-15.7 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 685

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND2	unassigned_transcript_4793	c.354T>C	p.Val118Val	synonymous_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND2	ENST00000361453.3	c.354T>C	p.Val118Val	synonymous_variant	Exon 1 of 1	6		ENSP00000355046.4

Frequencies

Mitomap GenBank AF: 0.0048 AC: 292

Gnomad homoplasmic AF: 0.012 AC: 685 AN: 56418

Gnomad heteroplasmic AF: 0.00011 AC: 6 AN: 56418

Alfa AF: 0.00301 Hom.: 13

Mitomap

No disease associated.

ClinVar

Significance: Likely benign

Submissions summary: Benign:1

Revision: criteria provided, single submitter

Submissions by phenotype

not provided Benign:1

Jul 08, 2015

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

Significance: Likely benign

Review Status: criteria provided, single submitter

Collection Method: clinical testing

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Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-16
Mutation Taster		=87/13	polymorphism

Other links and lift over

dbSNP: rs878853062; hg19: chrM-4824;