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NM_000251.3(MSH2):c.116G>C (p.Arg39Pro) AND Hereditary cancer-predisposing syndrome

Germline classification:
Uncertain significance (2 submissions)
Last evaluated:
Nov 1, 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:
RCV000132280.10

Allele description [Variation Report for NM_000251.3(MSH2):c.116G>C (p.Arg39Pro)]

NM_000251.3(MSH2):c.116G>C (p.Arg39Pro)

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.116G>C (p.Arg39Pro)
HGVS:
  • NC_000002.12:g.47403307G>C
  • NG_007110.2:g.5184G>C
  • NM_000251.3:c.116G>CMANE SELECT
  • NM_001258281.1:c.-30-53G>C
  • NP_000242.1:p.Arg39Pro
  • NP_000242.1:p.Arg39Pro
  • LRG_218t1:c.116G>C
  • LRG_218:g.5184G>C
  • LRG_218p1:p.Arg39Pro
  • NC_000002.11:g.47630446G>C
  • NM_000251.1:c.116G>C
  • NM_000251.2:c.116G>C
  • p.R39P
Protein change:
R39P
Links:
dbSNP: rs587782759
NCBI 1000 Genomes Browser:
rs587782759
Molecular consequence:
  • NM_001258281.1:c.-30-53G>C - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000251.3:c.116G>C - missense variant - [Sequence Ontology: SO:0001583]

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

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000187364Ambry Genetics
criteria provided, single submitter

(Ambry Variant Classification Scheme 2023)		Uncertain significance
(Nov 1, 2022) 		germlineclinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link,

SCV000908268Color Diagnostics, LLC DBA Color Health
criteria provided, single submitter

(ACMG Guidelines, 2015)		Uncertain significance
(Jun 12, 2019) 		germlineclinical testing

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

Help

Summary from all submissions

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

Citations

PubMed

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]
PMID:
28135145
PMCID:
PMC5455355

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
See all PubMed Citations (3)

Details of each submission

From Ambry Genetics, SCV000187364.9

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (2)

Description

The p.R39P variant (also known as c.116G>C), located in coding exon 1 of the MSH2 gene, results from a G to C substitution at nucleotide position 116. The arginine at codon 39 is replaced by proline, an amino acid with dissimilar properties. This alteration, called a variant of uncertain significance, was detected in a cohort of 1058 colorectal cancer patients who underwent multi-gene panel testing (Yurgelun MB et al. J. Clin. Oncol., 2017 Apr;35:1086-1095). 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 highly conserved in available vertebrate species. In addition, this alteration is predicted to be deleterious 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
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

From Color Diagnostics, LLC DBA Color Health, SCV000908268.2

#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 29, 2024