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NM_000251.3(MSH2):c.565G>A (p.Ala189Thr) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (1 submission)
Last evaluated:
Oct 18, 2022
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:
RCV001024381.2

Allele description [Variation Report for NM_000251.3(MSH2):c.565G>A (p.Ala189Thr)]

NM_000251.3(MSH2):c.565G>A (p.Ala189Thr)

Gene:
MSH2:mutS homolog 2 [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
2p21
Genomic location:
Preferred name:
NM_000251.3(MSH2):c.565G>A (p.Ala189Thr)
HGVS:
  • NC_000002.12:g.47410292G>A
  • NG_007110.2:g.12169G>A
  • NM_000251.3:c.565G>AMANE SELECT
  • NM_001258281.1:c.367G>A
  • NP_000242.1:p.Ala189Thr
  • NP_000242.1:p.Ala189Thr
  • NP_001245210.1:p.Ala123Thr
  • LRG_218t1:c.565G>A
  • LRG_218:g.12169G>A
  • LRG_218p1:p.Ala189Thr
  • NC_000002.11:g.47637431G>A
  • NM_000251.1:c.565G>A
  • NM_000251.2:c.565G>A
Protein change:
A123T
Links:
dbSNP: rs63750821
NCBI 1000 Genomes Browser:
rs63750821
Molecular consequence:
  • NM_000251.3:c.565G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001258281.1:c.367G>A - missense variant - [Sequence Ontology: SO:0001583]
Observations:
1

Condition(s)

Name:
Hereditary cancer-predisposing syndrome
Synonyms:
Neoplastic Syndromes, Hereditary; Tumor predisposition; Cancer predisposition; See all synonyms [MedGen]
Identifiers:
MONDO: MONDO:0015356; MeSH: D009386; MedGen: C0027672

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Assertion and evidence details

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Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV001186385Ambry Genetics
criteria provided, single submitter

(Ambry General Variant Classification Scheme_2022)		Uncertain significance
(Oct 18, 2022) 		germlineclinical testing

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

Citation Link

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Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing

Citations

PubMed

Massively parallel functional testing of MSH2 missense variants conferring Lynch syndrome risk.

Jia X, Burugula BB, Chen V, Lemons RM, Jayakody S, Maksutova M, Kitzman JO.

Am J Hum Genet. 2021 Jan 7;108(1):163-175. doi: 10.1016/j.ajhg.2020.12.003. Epub 2020 Dec 23.

PubMed [citation]
PMID:
33357406
PMCID:
PMC7820803

Details of each submission

From Ambry Genetics, SCV001186385.3

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided1not providednot providedclinical testing PubMed (1)

Description

The p.A189T variant (also known as c.565G>A), located in coding exon 3 of the MSH2 gene, results from a G to A substitution at nucleotide position 565. The alanine at codon 189 is replaced by threonine, an amino acid with similar properties. In a massively parallel cell-based functional assay testing susceptibility to a DNA damaging agent, 6-thioguanine (6-TG), this variant was reported to be functionally neutral (Jia X et al. Am J Hum Genet, 2021 01;108:163-175). This amino acid position is well conserved in available vertebrate species. In addition, this alteration is predicted to be tolerated by in silico analysis. Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknown1not providednot provided1not providednot providednot provided

Last Updated: Feb 28, 2024