NM_020745.4(AARS2):c.2525G>A (p.Arg842Gln) AND not provided

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Dec 3, 2021
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:: RCV001922478.11

Allele description [Variation Report for NM_020745.4(AARS2):c.2525G>A (p.Arg842Gln)]

NM_020745.4(AARS2):c.2525G>A (p.Arg842Gln)

Gene:

AARS2:alanyl-tRNA synthetase 2, mitochondrial [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

6p21.1

Genomic location:

Preferred name:

NM_020745.4(AARS2):c.2525G>A (p.Arg842Gln)

HGVS:

NC_000006.12:g.44302133C>T
NG_028283.4:g.790046C>T
NG_031952.2:g.16214G>A
NM_020745.4:c.2525G>AMANE SELECT
NP_065796.2:p.Arg842Gln
NC_000006.11:g.44269870C>T
NG_031952.1:g.16194G>A

Protein change:

R842Q

Links:

dbSNP: rs199677657

NCBI 1000 Genomes Browser:

rs199677657

Molecular consequence:

NM_020745.4:c.2525G>A - missense variant - [Sequence Ontology: SO:0001583]

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
SCV002171074	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Uncertain significance (Dec 3, 2021)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 31692161, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV002171074

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Uncertain significance
(Dec 3, 2021)

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	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

A diagnostic ceiling for exome sequencing in cerebellar ataxia and related neurological disorders.

Ngo KJ, Rexach JE, Lee H, Petty LE, Perlman S, Valera JM, Deignan JL, Mao Y, Aker M, Posey JE, Jhangiani SN, Coban-Akdemir ZH, Boerwinkle E, Muzny D, Nelson AB, Hassin-Baer S, Poke G, Neas K, Geschwind MD, Grody WW, Gibbs R, Geschwind DH, et al.

Hum Mutat. 2020 Feb;41(2):487-501. doi: 10.1002/humu.23946. Epub 2019 Nov 25.

PubMed [citation]

PMID:: 31692161
PMCID:: PMC7182470

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 Labcorp Genetics (formerly Invitae), Labcorp, SCV002171074.2

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

Description

This sequence change replaces arginine, which is basic and polar, with glutamine, which is neutral and polar, at codon 842 of the AARS2 protein (p.Arg842Gln). This variant is present in population databases (rs199677657, gnomAD 0.006%). This missense change has been observed in individual(s) with cerebellar ataxia (PMID: 31692161). 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 not expected to disrupt AARS2 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.

#	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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