rs28357984

Variant names:

• chrM-5178-C-A
• rs28357984
• ENST00000361453.3:c.709C>A

Your query was ambiguous. Multiple possible variants found:

• chrM-5178-C-A
• chrM-5178-C-T

Variant summary

Our verdict is Benign. The variant received -17 ACMG points: 0P and 17B. BP4 BP6_Very_Strong BA1

The ENST00000361453.3(MT-ND2):​c.709C>A​(p.Leu237Met) variant causes a missense change involving the alteration of a non-conserved nucleotide. In-silico tool predicts a benign outcome for this variant. 7/11 in silico tools predict a benign outcome for this variant. Variant has been reported in ClinVar as Benign (★★).

• Frequency: Mitomap GenBank: 𝑓 0.045 (AC: 2752)
• Consequence: MT-ND2 ENST00000361453.3 missense
• Scores: Apogee2 Benign 0.031
• Clinical Significance: Benign criteria provided, multiple submitters, no conflicts B:2 Longevity-/-Extraversion-/-diabetes-/-AMS-protection-/-blood-iron-metabolism-/-correlation-with-myocardial-infarction-/-atherosclerosis
• Conservation: PhyloP100: -4.27
• Publications: 39 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 -17 ACMG points.

• BP4: Apogee2 supports a benign effect, 0.03096441 < 0.5 .
• BP6: Variant M-5178-C-A is Benign according to our data. Variant chrM-5178-C-A is described in ClinVar as Benign. ClinVar VariationId is 692551.Status of the report is criteria_provided_multiple_submitters_no_conflicts, 2 stars.
• BA1: High frequency in mitomap database: 0.045

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

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
There are no transcript annotations for this variant.

Ensembl Transcripts

Selected	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	MT-ND2	ENST00000361453.3	TSL:6	c.709C>A	p.Leu237Met	missense	Exon 1 of 1	ENSP00000355046.4

Frequencies

Mitomap GenBank AF: 0.045 AC: 2752

Gnomad homoplasmic AF: 0.011 AC: 603 AN: 56426

Gnomad heteroplasmic AF: 0.0 AC: 0 AN: 56426

Alfa AF: 0.00636 Hom.: 28

Mitomap

Disease(s): Longevity-/-Extraversion-/-diabetes-/-AMS-protection-/-blood-iron-metabolism-/-correlation-with-myocardial-infarction-/-atherosclerosis

Status: Reported

ClinVar

ClinVar submissions as Germline

Significance: Benign

Revision: criteria provided, multiple submitters, no conflicts

Pathogenic	VUS	Benign	Condition
-	-	1	Leigh syndrome (1)
-	-	1	not specified (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
Apogee2	Benign	0.031
Hmtvar	Pathogenic	0.63
AlphaMissense	Benign	0.063
BayesDel_addAF	Benign	-0.23	T
DEOGEN2	Benign	0.011	T
LIST_S2	Benign	0.72	T
MutationAssessor	Benign	1.1	L
PhyloP100		-4.3
PROVEAN	Benign	-0.39	N
GERP RS		-10
Varity_R		0.41
Mutation Taster		=97/3	polymorphism

Other links and lift over

dbSNP: rs28357984; hg19: chrM-5179;