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NM_000535.7(PMS2):c.59G>A (p.Arg20Gln) AND Endometrial carcinoma

Germline classification:
Benign (1 submission)
Review status:
(0/4) 0 stars out of maximum of 4 stars
no assertion criteria provided
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:
RCV001353558.10

Allele description [Variation Report for NM_000535.7(PMS2):c.59G>A (p.Arg20Gln)]

NM_000535.7(PMS2):c.59G>A (p.Arg20Gln)

Gene:
PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
7p22.1
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.59G>A (p.Arg20Gln)
HGVS:
  • NC_000007.14:g.6005996C>T
  • NG_008466.1:g.8111G>A
  • NG_050738.1:g.1746C>T
  • NM_000535.7:c.59G>AMANE SELECT
  • NM_001322003.2:c.-347G>A
  • NM_001322004.2:c.-242-1938G>A
  • NM_001322005.2:c.-347G>A
  • NM_001322006.2:c.59G>A
  • NM_001322007.2:c.-157G>A
  • NM_001322008.2:c.-52-1938G>A
  • NM_001322009.2:c.-347G>A
  • NM_001322010.2:c.-242-1938G>A
  • NM_001322011.2:c.-826G>A
  • NM_001322012.2:c.-826G>A
  • NM_001322013.2:c.-347G>A
  • NM_001322014.2:c.59G>A
  • NM_001322015.2:c.-426G>A
  • NP_000526.2:p.Arg20Gln
  • NP_001308935.1:p.Arg20Gln
  • NP_001308943.1:p.Arg20Gln
  • LRG_161t1:c.59G>A
  • LRG_161:g.8111G>A
  • NC_000007.13:g.6045627C>T
  • NM_000535.5:c.59G>A
  • NM_000535.6:c.59G>A
  • NR_136154.1:n.146G>A
  • P54278:p.Arg20Gln
  • p.R20Q
Protein change:
R20Q
Links:
UniProtKB: P54278#VAR_004469; dbSNP: rs10254120
NCBI 1000 Genomes Browser:
rs10254120
Molecular consequence:
  • NM_001322003.2:c.-347G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322005.2:c.-347G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322007.2:c.-157G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322009.2:c.-347G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322011.2:c.-826G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322012.2:c.-826G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322013.2:c.-347G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322015.2:c.-426G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322004.2:c.-242-1938G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322008.2:c.-52-1938G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_001322010.2:c.-242-1938G>A - intron variant - [Sequence Ontology: SO:0001627]
  • NM_000535.7:c.59G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.59G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.59G>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.146G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:
Endometrial carcinoma
Synonyms:
Endometrial carcinoma, somatic
Identifiers:
MONDO: MONDO:0002447; MedGen: C0476089; OMIM: 608089; Human Phenotype Ontology: HP:0012114

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Assertion and evidence details

Help
Submission AccessionSubmitterReview Status
(Assertion method)		Clinical Significance
(Last evaluated)		OriginMethodCitations
SCV000592920Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR)

See additional submitters

no assertion criteria provided
Benignunknownclinical testing

Help

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedunknownyes0not providednot providednot providednot providedclinical testing

Details of each submission

From Department of Pathology and Laboratory Medicine, Sinai Health System - The Canadian Open Genetics Repository (COGR), SCV000592920.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not provided0not providednot providedclinical testingnot provided

Description

PMS2, EXON 2, c.59G>A, p.Arg20Gln, Benign (ACMG 5) In the (8072530_Nicolaides_1994, 16472587_Hendriks_2006 , 18768816_Marionvic-Terzic_2008 21239990_Pastrello_2011 , 22703879_Johnston_2012 , 23709753_Borras_2013 23981578_Wang_2013, 24618965_Dewey_2014, 24689082_Hansen_2014, 24728327_Bodian_2014, 22949387_Thompson_2013) articles, a total of 8 proband alleles of 112 (frequency: 0.027) tested positive for the variant and of the controls a total of 31 alleles of 379 tested positive (frequency: 0.082). In 22703879_johnston_2012, the variant was found in 77 of 572 individuals not included in the previous numbers; many of the articles suggest that the variant is a polymorphism and is benign. The variant was also identified in dbSNP (ID: rs10254120 ) “With untested allele”, with a minor allele frequency of 7.024% (1000 Genomes Project), HGMD, MutDB, “Mismatch Repair Genes Variant Database”, “MMR Gene Unclassified Variants Database”, “InSiGHT Colon Cancer Database”, ClinVar database. In the ClinVar database, 5 separate submitters classify the variant as benign. This variant was identified in the 1000 Genomes Project in 153 of 2178 chromosomes (frequency: 0.07), Exome Variant Server project in 272 of 4320 European American (frequency: 0.06) and in 246 of 2714 African American alleles (frequency: 0.09), increasing the likelihood that this is/may be a low frequency benign variant in certain populations of origin. The p.Arg20 residue is not conserved in mammals and the variant amino acid Glycine (Gly) is present in Trichoplax adhaerens, increasing the likelihood that this variant does not have clinical significance. Computational analyses (PolyPhen-2, SIFT, AlignGVGD, BLOSUM, MutationTaster) provide inconsistent predictions regarding the impact to the protein and this information is not very predictive of pathogenicity. The c.59G>A variant occurs outside of the splicing consensus sequence and in silico or computational prediction software (SpliceSiteFinder, MaxEntScan, NNSPLICE, GeneSplicer, HumanSpliceFinder) does not predict a difference in splicing in 5 of 5 different programs. (However, this information is not predictive enough to rule out pathogenicity.) In summary, based on the above information, this variant meets our laboratory's criteria to be classified as benign.

#SampleMethodObservation
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1unknownyesnot providednot providednot provided0not providednot providednot provided

Last Updated: Oct 13, 2024