NM_000535.7(PMS2):c.1909C>T (p.Gln637Ter) AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Pathogenic (Last evaluated: Jan 17, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:

Allele description [Variation Report for NM_000535.7(PMS2):c.1909C>T (p.Gln637Ter)]

NM_000535.7(PMS2):c.1909C>T (p.Gln637Ter)

PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
single nucleotide variant
Cytogenetic location:
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.1909C>T (p.Gln637Ter)
  • NC_000007.14:g.5986856G>A
  • NG_008466.1:g.27251C>T
  • NM_000535.7:c.1909C>TMANE SELECT
  • NM_001322003.2:c.1504C>T
  • NM_001322004.2:c.1504C>T
  • NM_001322005.2:c.1504C>T
  • NM_001322006.2:c.1753C>T
  • NM_001322007.2:c.1591C>T
  • NM_001322008.2:c.1591C>T
  • NM_001322009.2:c.1504C>T
  • NM_001322010.2:c.1348C>T
  • NM_001322011.2:c.976C>T
  • NM_001322012.2:c.976C>T
  • NM_001322013.2:c.1336C>T
  • NM_001322014.2:c.1909C>T
  • NM_001322015.2:c.1600C>T
  • NP_000526.2:p.Gln637Ter
  • NP_001308932.1:p.Gln502Ter
  • NP_001308933.1:p.Gln502Ter
  • NP_001308934.1:p.Gln502Ter
  • NP_001308935.1:p.Gln585Ter
  • NP_001308936.1:p.Gln531Ter
  • NP_001308937.1:p.Gln531Ter
  • NP_001308938.1:p.Gln502Ter
  • NP_001308939.1:p.Gln450Ter
  • NP_001308940.1:p.Gln326Ter
  • NP_001308941.1:p.Gln326Ter
  • NP_001308942.1:p.Gln446Ter
  • NP_001308943.1:p.Gln637Ter
  • NP_001308944.1:p.Gln534Ter
  • LRG_161t1:c.1909C>T
  • LRG_161:g.27251C>T
  • NC_000007.13:g.6026487G>A
  • NM_000535.5:c.1909C>T
  • NM_000535.6:c.1909C>T
  • NR_136154.1:n.1996C>T
Protein change:
dbSNP: rs1554297125
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NR_136154.1:n.1996C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
  • NM_000535.7:c.1909C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322003.2:c.1504C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322004.2:c.1504C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322005.2:c.1504C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322006.2:c.1753C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322007.2:c.1591C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322008.2:c.1591C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322009.2:c.1504C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322010.2:c.1348C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322011.2:c.976C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322012.2:c.976C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322013.2:c.1336C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322014.2:c.1909C>T - nonsense - [Sequence Ontology: SO:0001587]
  • NM_001322015.2:c.1600C>T - nonsense - [Sequence Ontology: SO:0001587]


Hereditary nonpolyposis colorectal neoplasms
MedGen: C0009405; Orphanet: 443090

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV001391451Invitaecriteria provided, single submitter
(Jan 17, 2020)
germlineclinical testing

PubMed (3)
[See all records that cite these PMIDs]

Summary from all submissions

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



Paediatric intestinal cancer and polyposis due to bi-allelic PMS2 mutations: case series, review and follow-up guidelines.

Herkert JC, Niessen RC, Olderode-Berends MJ, Veenstra-Knol HE, Vos YJ, van der Klift HM, Scheenstra R, Tops CM, Karrenbeld A, Peters FT, Hofstra RM, Kleibeuker JH, Sijmons RH.

Eur J Cancer. 2011 May;47(7):965-82. doi: 10.1016/j.ejca.2011.01.013. Epub 2011 Mar 4. Review.

PubMed [citation]

Application of a 5-tiered scheme for standardized classification of 2,360 unique mismatch repair gene variants in the InSiGHT locus-specific database.

Thompson BA, Spurdle AB, Plazzer JP, Greenblatt MS, Akagi K, Al-Mulla F, Bapat B, Bernstein I, Capellá G, den Dunnen JT, du Sart D, Fabre A, Farrell MP, Farrington SM, Frayling IM, Frebourg T, Goldgar DE, Heinen CD, Holinski-Feder E, Kohonen-Corish M, Robinson KL, Leung SY, et al.

Nat Genet. 2014 Feb;46(2):107-115. doi: 10.1038/ng.2854. Epub 2013 Dec 22.

PubMed [citation]
See all PubMed Citations (3)

Details of each submission

From Invitae, SCV001391451.2

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (3)


This sequence change creates a premature translational stop signal (p.Gln637*) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. This variant is not present in population databases (ExAC no frequency). This variant has not been reported in the literature in individuals with PMS2-related conditions. ClinVar contains an entry for this variant (Variation ID: 496033). Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as Pathogenic.

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

Last Updated: Nov 27, 2021

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