NM_004549.6(NDUFC2):c.346_*7del (p.His116fs) AND Mitochondrial complex 1 deficiency, nuclear type 36

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Jan 29, 2021
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of clinical impact:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Somatic classification of oncogenicity:: None
Review status:: (0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided

Record status:: current
Accession:: RCV001290294.1

Allele description [Variation Report for NM_004549.6(NDUFC2):c.346_*7del (p.His116fs)]

NM_004549.6(NDUFC2):c.346_*7del (p.His116fs)

Genes:

NDUFC2:NADH:ubiquinone oxidoreductase subunit C2 [Gene - OMIM - HGNC]
NDUFC2-KCTD14:NDUFC2-KCTD14 readthrough [Gene - HGNC]

Variant type:

Deletion

Cytogenetic location:

11q14.1

Genomic location:

Preferred name:

NM_004549.6(NDUFC2):c.346_*7del (p.His116fs)

HGVS:

NC_000011.10:g.78069983_78070004del
NM_001203260.2:c.310+2997_310+3018del
NM_001203261.2:c.310+2997_310+3018del
NM_001203262.2:c.166+9578_166+9599del
NM_001204054.3:c.230-91_230-70del
NM_001204055.2:c.277_*7del
NM_004549.6:c.346_*7delMANE SELECT
NP_001190984.1:p.His93fs
NP_004540.1:p.His116fs
NC_000011.9:g.77781029_77781050del

Protein change:

H116fs

Links:

OMIM: 603845.0001; dbSNP: rs1858924087

NCBI 1000 Genomes Browser:

rs1858924087

Molecular consequence:

NM_001204055.2:c.277_*7del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_004549.6:c.346_*7del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001203260.2:c.310+2997_310+3018del - intron variant - [Sequence Ontology: SO:0001627]
NM_001203261.2:c.310+2997_310+3018del - intron variant - [Sequence Ontology: SO:0001627]
NM_001203262.2:c.166+9578_166+9599del - intron variant - [Sequence Ontology: SO:0001627]
NM_001204054.3:c.230-91_230-70del - intron variant - [Sequence Ontology: SO:0001627]

Condition(s)

Name:: Mitochondrial complex 1 deficiency, nuclear type 36
Synonyms:: MITOCHONDRIAL COMPLEX I DEFICIENCY, NUCLEAR TYPE 36
Identifiers:: MONDO: MONDO:0030902; MedGen: C5436935; OMIM: 619170

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001478325	OMIM	no assertion criteria provided	Pathogenic (Jan 29, 2021)	germline	literature only	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001478325

OMIM

no assertion criteria provided

Pathogenic
(Jan 29, 2021)

germline

literature only

PubMed (1)
[See all records that cite this PMID]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	not provided	not provided	not provided	not provided	not provided	not provided	literature only

Citations

PubMed

Bi-allelic pathogenic variants in NDUFC2 cause early-onset Leigh syndrome and stalled biogenesis of complex I.

Alahmad A, Nasca A, Heidler J, Thompson K, Oláhová M, Legati A, Lamantea E, Meisterknecht J, Spagnolo M, He L, Alameer S, Hakami F, Almehdar A, Ardissone A, Alston CL, McFarland R, Wittig I, Ghezzi D, Taylor RW.

EMBO Mol Med. 2020 Nov 6;12(11):e12619. doi: 10.15252/emmm.202012619. Epub 2020 Sep 24.

PubMed [citation]

PMID:: 32969598
PMCID:: PMC7645371

Details of each submission

From OMIM, SCV001478325.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	literature only	PubMed (1)

Description

In a 6-year-old girl (patient 1), born of consanguineous Saudi Arabian parents (family 1), with mitochondrial complex I deficiency nuclear type 36 (MC1DN36; 619170), Alahmad et al. (2020) identified a homozygous 22-bp deletion (c.346_*7del, NM_004549.6) in the last exon of the NDUFC2 gene. The mutation was predicted to cause a stop-loss variant (His116_Arg119delins21). The mutation, which was found by whole-genome sequencing and confirmed by Sanger sequencing, segregated with the disorder in the family. It was not present in the gnomAD database. Patient fibroblasts showed isolated complex I deficiency (16% residual activity), decreased levels of NDUFC2 mRNA (43% of controls), and defects in the assembly of complex I. These defects could be partially rescued by expression of wildtype NDUFC2. The patient had a similarly affected sib who died; tissue was not available from that patient.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	not provided	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Dec 9, 2023

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