NM_005138.3(SCO2):c.268C>T (p.Arg90Ter) AND not provided

Germline classification:: Pathogenic (1 submission)
Last evaluated:: May 13, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001851688.3

Allele description [Variation Report for NM_005138.3(SCO2):c.268C>T (p.Arg90Ter)]

NM_005138.3(SCO2):c.268C>T (p.Arg90Ter)

Genes:

NCAPH2:non-SMC condensin II complex subunit H2 [Gene - OMIM - HGNC]
SCO2:synthesis of cytochrome C oxidase 2 [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_005138.3(SCO2):c.268C>T (p.Arg90Ter)

Other names:

p.Arg90*

HGVS:

NC_000022.11:g.50524144G>A
NG_011860.1:g.10942C>T
NG_016235.1:g.7296C>T
NG_021419.1:g.20929G>A
NM_001169109.2:c.268C>T
NM_001169110.1:c.268C>T
NM_001169111.2:c.268C>T
NM_001185011.2:c.*769G>A
NM_005138.3:c.268C>TMANE SELECT
NM_152299.4:c.*769G>AMANE SELECT
NP_001162580.1:p.Arg90Ter
NP_001162581.1:p.Arg90Ter
NP_001162582.1:p.Arg90Ter
NP_005129.2:p.Arg90Ter
NP_005129.2:p.Arg90Ter
LRG_727:g.10942C>T
NC_000022.10:g.50962573G>A
NM_005138.2:c.268C>T

Protein change:

R90*; ARG90TER

Links:

OMIM: 604272.0005; dbSNP: rs74315512

NCBI 1000 Genomes Browser:

rs74315512

Molecular consequence:

NM_001185011.2:c.*769G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152299.4:c.*769G>A - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001169109.2:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001169110.1:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001169111.2:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_005138.3:c.268C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV002192109	Invitae	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (May 13, 2023)	germline	clinical testing	PubMed (6) [See all records that cite these PMIDs] 10545952, 15210538, 16765077, 23719228, 10749987, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002192109

Invitae

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(May 13, 2023)

germline

clinical testing

PubMed (6)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

Fatal infantile cardioencephalomyopathy with COX deficiency and mutations in SCO2, a COX assembly gene.

Papadopoulou LC, Sue CM, Davidson MM, Tanji K, Nishino I, Sadlock JE, Krishna S, Walker W, Selby J, Glerum DM, Coster RV, Lyon G, Scalais E, Lebel R, Kaplan P, Shanske S, De Vivo DC, Bonilla E, Hirano M, DiMauro S, Schon EA.

Nat Genet. 1999 Nov;23(3):333-7.

PubMed [citation]

PMID:: 10545952

Association of mutations in SCO2, a cytochrome c oxidase assembly gene, with early fetal lethality.

Tay SK, Shanske S, Kaplan P, DiMauro S.

Arch Neurol. 2004 Jun;61(6):950-2.

PubMed [citation]

PMID:: 15210538

See all PubMed Citations (6)

Details of each submission

From Invitae, SCV002192109.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (6)

Description

For these reasons, this variant has been classified as Pathogenic. This variant disrupts a region of the SCO2 protein in which other variant(s) (p.Glu140Lys) have been determined to be pathogenic (PMID: 10545952, 15210538, 16765077, 23719228). This suggests that this is a clinically significant region of the protein, and that variants that disrupt it are likely to be disease-causing. ClinVar contains an entry for this variant (Variation ID: 5682). This premature translational stop signal has been observed in individual(s) with autosomal recessive cardioencephalomyopathy (PMID: 10749987). It has also been observed to segregate with disease in related individuals. This variant is present in population databases (rs74315512, gnomAD 0.003%). This sequence change creates a premature translational stop signal (p.Arg90*) in the SCO2 gene. While this is not anticipated to result in nonsense mediated decay, it is expected to disrupt the last 177 amino acid(s) of the SCO2 protein.

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

Last Updated: Feb 20, 2024

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