rs41419549

Variant names:

• chrM-5004-T-C
• rs41419549
• ENST00000361453.3:c.535T>C

Variant summary

Our verdict is Benign. The variant received -9 ACMG points: 0P and 9B. BP7 BS1 BS2

The ENST00000361453.3(MT-ND2):​c.535T>C​(p.Leu179Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. No clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar.

• Frequency: Mitomap GenBank: 𝑓 0.0074 (AC: 452)
• Consequence: MT-ND2 ENST00000361453.3 synonymous
• Clinical Significance: Not reported in ClinVar No linked disesase in Mitomap
• Conservation: PhyloP100: -4.82
• 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]

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 -9 ACMG points.

• BP7: Synonymous conserved (PhyloP=-4.82 with no splicing effect.
• BS1: High frequency in mitomap database: 0.0074
• BS2: High AC in GnomadMitoHomoplasmic at 593

Transcripts

RefSeq

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	MANE	Protein	UniProt
ND2	unassigned_transcript_4793	c.535T>C	p.Leu179Leu	synonymous_variant	Exon 1 of 1

Ensembl

Gene	Transcript	HGVSc	HGVSp	Effect	Exon rank	TSL	MANE	Protein	Appris	UniProt
MT-ND2	ENST00000361453.3	c.535T>C	p.Leu179Leu	synonymous_variant	Exon 1 of 1	6		ENSP00000355046.4

Frequencies

Mitomap GenBank AF: 0.0074 AC: 452

Gnomad homoplasmic AF: 0.011 AC: 593 AN: 56418

Gnomad heteroplasmic AF: 0.000053 AC: 3 AN: 56418

Alfa AF: 0.00656 Hom.: 151

Mitomap

No disease associated.

ClinVar

Not reported in ClinVar

Computational scores

Source: dbNSFP v4.3

Name	Calibrated prediction	Score	Prediction
PhyloP100		-4.8
Mutation Taster		=84/16	polymorphism

Other links and lift over

dbSNP: rs41419549; hg19: chrM-5005;