NM_005138.3(SCO2):c.244_246del (p.Lys82del) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (2 submissions)
Last evaluated:: Jul 29, 2022
Review status:: criteria provided, conflicting classifications

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:: RCV001576864.7

Allele description [Variation Report for NM_005138.3(SCO2):c.244_246del (p.Lys82del)]

NM_005138.3(SCO2):c.244_246del (p.Lys82del)

Genes:

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

Variant type:

Deletion

Cytogenetic location:

22q13.33

Genomic location:

Preferred name:

NM_005138.3(SCO2):c.244_246del (p.Lys82del)

HGVS:

NC_000022.11:g.50524168_50524170del
NG_011860.1:g.10918_10920del
NG_016235.1:g.7272_7274del
NG_021419.1:g.20953_20955del
NM_001169109.2:c.244_246del
NM_001169110.1:c.244_246del
NM_001169111.2:c.244_246del
NM_001185011.2:c.*793_*795del
NM_005138.3:c.244_246delMANE SELECT
NM_152299.4:c.*793_*795delMANE SELECT
NP_001162580.1:p.Lys82del
NP_001162581.1:p.Lys82del
NP_001162582.1:p.Lys82del
NP_005129.2:p.Lys82del
LRG_727:g.10918_10920del
NC_000022.10:g.50962595_50962597del
NC_000022.10:g.50962597_50962599del
NM_005138.2:c.244_246delAAG

Protein change:

K82del

Links:

dbSNP: rs757005556

NCBI 1000 Genomes Browser:

rs757005556

Molecular consequence:

NM_001185011.2:c.*793_*795del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_152299.4:c.*793_*795del - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
NM_001169109.2:c.244_246del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001169110.1:c.244_246del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_001169111.2:c.244_246del - inframe_deletion - [Sequence Ontology: SO:0001822]
NM_005138.3:c.244_246del - inframe_deletion - [Sequence Ontology: SO:0001822]

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

Recent activity

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metal ABC transporter substrate-binding protein [Paraburkholderia acidiphila]
metal ABC transporter substrate-binding protein [Paraburkholderia acidiphila]
gi|1787164466|gnl|PRJNA534068|FAZ97 0|gb|QGZ58484.1|

Protein
LOC126743809 [Anthonomus grandis grandis]
LOC126743809 [Anthonomus grandis grandis]
Gene ID:126743809

Gene
LOC125436770 [Sphaerodactylus townsendi]
LOC125436770 [Sphaerodactylus townsendi]
Gene ID:125436770

Gene

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001804133	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Likely pathogenic (Apr 15, 2019)	germline	clinical testing	Citation Link,
SCV002218750	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Jul 29, 2022)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 23719228, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001804133

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Likely pathogenic
(Apr 15, 2019)

germline

clinical testing

Citation Link,

SCV002218750

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Jul 29, 2022)

germline

clinical testing

PubMed (2)
[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	yes	not provided	not provided	not provided	not provided	not provided	clinical testing
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The natural history of SCO2 deficiency in 36 Polish children confirmed the genotype-phenotype correlation.

Pronicka E, Piekutowska-Abramczuk D, Szymańska-Dębińska T, Bielecka L, Kowalski P, Luczak S, Karkucińska-Więckowska A, Migdał M, Kubalska J, Zimowski J, Jamroz E, Wierzba J, Sykut-Cegielska J, Pronicki M, Zaremba J, Krajewska-Walasek M.

Mitochondrion. 2013 Nov;13(6):810-6. doi: 10.1016/j.mito.2013.05.007. Epub 2013 May 26.

PubMed [citation]

PMID:: 23719228

Sherloc: a comprehensive refinement of the ACMG-AMP variant classification criteria.

Nykamp K, Anderson M, Powers M, Garcia J, Herrera B, Ho YY, Kobayashi Y, Patil N, Thusberg J, Westbrook M; Invitae Clinical Genomics Group., Topper S.

Genet Med. 2017 Oct;19(10):1105-1117. doi: 10.1038/gim.2017.37. Epub 2017 May 11. Erratum in: Genet Med. 2020 Jan;22(1):240. doi: 10.1038/s41436-019-0624-9.

PubMed [citation]

PMID:: 28492532
PMCID:: PMC5632818

Details of each submission

From GeneDx, SCV001804133.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

Description

Identified in a patient with SCO2 deficiency (described as g.1367_1369delAAG due to alternate nomenclature) in the presence of a second SCO2 pathogenic variant in published literature (Pronicka et al., 2013); In silico analysis, which includes protein predictors and evolutionary conservation, supports a deleterious effect; In-frame deletion of 1 amino acid in a non-repeat region; Not observed at a significant frequency in large population cohorts (Lek et al., 2016); This variant is associated with the following publications: (PMID: 23719228)

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

From Labcorp Genetics (formerly Invitae), Labcorp, SCV002218750.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

This variant, c.244_246del, results in the deletion of 1 amino acid(s) of the SCO2 protein (p.Lys82del), but otherwise preserves the integrity of the reading frame. This variant is present in population databases (rs757005556, gnomAD 0.005%). This variant has been observed in individual(s) with clinical features of cytochrome c oxidase deficiency (PMID: 23719228). This variant is also known as g.1367_1369delAAG (p.82delK). ClinVar contains an entry for this variant (Variation ID: 1208507). Experimental studies and prediction algorithms are not available or were not evaluated, and the functional significance of this variant is currently unknown. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

#	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: Sep 29, 2024

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