rs1556422960

Variant names:

• chrM-5177-G-A
• rs1556422960
• ENST00000361453.3:c.708G>A
• MT-ND2 p.Lys236Lys

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.708G>A​(p.Lys236Lys) 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 0.00060 (AC: 36)
• Consequence: MT-ND2 ENST00000361453.3 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1 No linked disesase in Mitomap
• Conservation: PhyloP100: 0.0460
• Publications: 0 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-5177-G-A is Benign according to our data. Variant chrM-5177-G-A is described in ClinVar as Likely_benign. ClinVar VariationId is 445705.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=0.046 with no splicing effect.
• BS2: High AC in GnomadMitoHomoplasmic at 62

Variant Effect in Transcripts

ACMG analysis was done for transcript: ENST00000361453.3. 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
There are no transcript annotations for this variant.

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND2	ENST00000361453.3	TSL:6	c.708G>A	p.Lys236Lys	synonymous	Exon 1 of 1	ENSP00000355046.4	P03891

Frequencies

Mitomap GenBank AF: 0.00060 AC: 36

Gnomad homoplasmic AF: 0.0011 AC: 62 AN: 56423

Gnomad heteroplasmic AF: 0.000071 AC: 4 AN: 56423

Alfa AF: 0.000223 Hom.: 1

Mitomap

No disease associated.

ClinVar

ClinVar submissions

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
PhyloP100		0.046
Mutation Taster		=96/4	polymorphism

MaxEntScan Visualizer can be used to analyze the impact of this mutation on the neighboring sequence.

Other links and lift over

dbSNP: rs1556422960;

hg19: chrM-5178;