NM_000030.3(AGXT):c.866G>A (p.Arg289His) AND not provided

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(2) (Last evaluated: Dec 8, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
3 submissions [Details]
Record status:
current
Accession:
RCV000587981.5

Allele description [Variation Report for NM_000030.3(AGXT):c.866G>A (p.Arg289His)]

NM_000030.3(AGXT):c.866G>A (p.Arg289His)

Gene:
AGXT:alanine--glyoxylate and serine--pyruvate aminotransferase [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2q37.3
Genomic location:
Preferred name:
NM_000030.3(AGXT):c.866G>A (p.Arg289His)
HGVS:
  • NC_000002.12:g.240877556G>A
  • NG_008005.1:g.13812G>A
  • NM_000030.3:c.866G>AMANE SELECT
  • NP_000021.1:p.Arg289His
  • NP_000021.1:p.Arg289His
  • NC_000002.11:g.241816973G>A
  • NM_000030.2:c.866G>A
Protein change:
R289H
Links:
dbSNP: rs61729604
NCBI 1000 Genomes Browser:
rs61729604
Molecular consequence:
  • NM_000030.3:c.866G>A - missense variant - [Sequence Ontology: SO:0001583]

Condition(s)

Identifiers:
MedGen: CN517202

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000232896EGL Genetic Diagnostics, Eurofins Clinical Diagnosticscriteria provided, single submitter
Uncertain significance
(Mar 30, 2015)
germlineclinical testing

Citation Link,

SCV000693981Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Uncertain significance
(Jun 26, 2017)
germlineclinical testing

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

LabCorp Variant Classification Summary - May 2015.docx,

Citation Link,

SCV001110251Invitaecriteria provided, single submitter
Likely benign
(Dec 8, 2020)
germlineclinical testing

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

Summary from all submissions

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

Citations

PubMed

Primary hyperoxaluria type 1: update and additional mutation analysis of the AGXT gene.

Williams EL, Acquaviva C, Amoroso A, Chevalier F, Coulter-Mackie M, Monico CG, Giachino D, Owen T, Robbiano A, Salido E, Waterham H, Rumsby G.

Hum Mutat. 2009 Jun;30(6):910-7. doi: 10.1002/humu.21021. Review.

PubMed [citation]
PMID:
19479957

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):240-242.

PubMed [citation]
PMID:
28492532
PMCID:
PMC5632818

Details of each submission

From EGL Genetic Diagnostics, Eurofins Clinical Diagnostics, SCV000232896.5

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testingnot provided
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000693981.1

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

Description

Variant summary: The AGXT c.866G>A (p.Arg289His) variant involves the alteration of a non-conserved nucleotide and is predicted to be benign by 2/3 in silico tools. This variant was found in 24/16730 control chromosomes from ExAC at a frequency of 0.0014345, which does not exceed the estimated maximal expected allele frequency of a pathogenic AGXT variant (0.0023717). This variant has been reported as a part of two complex alleles in patients with Primary Hyperoxaluria Type 1 (Williams_2009, Williams_2015). The complex allele p.[Arg289His;Leu298Pro] was found in homozygous state in two related patients with the neonatal form of disease and another complex allele p.[Arg289His;Leu359Pro] was found in one patient in compound heterozygous state with c.33dupC. The role of this variant in the complex allele - whether it is a driver mutation or a modifier- has yet to be elucidated. In ClinVar while one laboratory has classified it as pathogenic, another laboratory has classified it as VUS. Another missense variant at the same residue (p.Arg289Cys) has been classified as a VUS by a lab in ClinVar. There are no functional studies for this variant, to our knowledge. Taken together, this variant is currently classified as 'Variant of Unknown Significance'.

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

From Invitae, SCV001110251.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Sep 18, 2021

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