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NM_001098.3(ACO2):c.2036G>A (p.Arg679His) AND not provided

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Sep 6, 2022
Review status:
2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts
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:
RCV002958883.3

Allele description

NM_001098.3(ACO2):c.2036G>A (p.Arg679His)

Genes:
POLR3H:RNA polymerase III subunit H [Gene - OMIM - HGNC]
ACO2:aconitase 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
22q13.2
Genomic location:
Preferred name:
NM_001098.3(ACO2):c.2036G>A (p.Arg679His)
HGVS:
  • NC_000022.11:g.41527370G>A
  • NG_032143.1:g.63246G>A
  • NM_001018050.4:c.*1913C>TMANE SELECT
  • NM_001018052.4:c.*1913C>T
  • NM_001098.3:c.2036G>AMANE SELECT
  • NM_001282884.2:c.*1913C>T
  • NM_001282885.2:c.*1913C>T
  • NM_138338.5:c.*1913C>T
  • NP_001089.1:p.Arg679His
  • NC_000022.10:g.41923374G>A
Protein change:
R679H
Molecular consequence:
  • NM_001018050.4:c.*1913C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001018052.4:c.*1913C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001282884.2:c.*1913C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001282885.2:c.*1913C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_138338.5:c.*1913C>T - 3 prime UTR variant - [Sequence Ontology: SO:0001624]
  • NM_001098.3:c.2036G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Synonyms:
none provided
Identifiers:
MedGen: C3661900

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV003283242Invitae
criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))		Uncertain significance
(Sep 6, 2022) 		germlineclinical testing

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

SCV003762020GeneDx
criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)		Uncertain significance
(Jul 11, 2022) 		germlineclinical testing

Citation Link

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineyesnot providednot providednot providednot providednot providedclinical testing
not providedgermlineunknownnot providednot providednot providednot providednot providedclinical testing

Citations

PubMed

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 Invitae, SCV003283242.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)

Description

This variant has not been reported in the literature in individuals affected with ACO2-related conditions. This variant is not present in population databases (gnomAD no frequency). This sequence change replaces arginine, which is basic and polar, with histidine, which is basic and polar, at codon 679 of the ACO2 protein (p.Arg679His). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt ACO2 protein function. 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.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From GeneDx, SCV003762020.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided

Description

Not observed at significant frequency in large population cohorts (gnomAD); In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Has not been previously published as pathogenic or benign to our knowledge

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineyesnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 1, 2024