NM_000535.7(PMS2):c.433C>A (p.Gln145Lys) AND Hereditary nonpolyposis colorectal neoplasms

Clinical significance:Uncertain significance (Last evaluated: Dec 19, 2019)

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.433C>A (p.Gln145Lys)]

NM_000535.7(PMS2):c.433C>A (p.Gln145Lys)

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.433C>A (p.Gln145Lys)
  • NC_000007.14:g.6002557G>T
  • NG_008466.1:g.11550C>A
  • NM_000535.7:c.433C>AMANE SELECT
  • NM_001322003.2:c.28C>A
  • NM_001322004.2:c.28C>A
  • NM_001322005.2:c.28C>A
  • NM_001322006.2:c.433C>A
  • NM_001322007.2:c.115C>A
  • NM_001322008.2:c.115C>A
  • NM_001322009.2:c.28C>A
  • NM_001322010.2:c.28C>A
  • NM_001322011.2:c.-452C>A
  • NM_001322012.2:c.-452C>A
  • NM_001322013.2:c.28C>A
  • NM_001322014.2:c.433C>A
  • NM_001322015.2:c.124C>A
  • NP_000526.2:p.Gln145Lys
  • NP_001308932.1:p.Gln10Lys
  • NP_001308933.1:p.Gln10Lys
  • NP_001308934.1:p.Gln10Lys
  • NP_001308935.1:p.Gln145Lys
  • NP_001308936.1:p.Gln39Lys
  • NP_001308937.1:p.Gln39Lys
  • NP_001308938.1:p.Gln10Lys
  • NP_001308939.1:p.Gln10Lys
  • NP_001308942.1:p.Gln10Lys
  • NP_001308943.1:p.Gln145Lys
  • NP_001308944.1:p.Gln42Lys
  • LRG_161t1:c.433C>A
  • LRG_161:g.11550C>A
  • NC_000007.13:g.6042188G>T
  • NM_000535.5:c.433C>A
  • NM_000535.6:c.433C>A
  • NR_136154.1:n.520C>A
Protein change:
dbSNP: rs786204133
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_001322011.2:c.-452C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_001322012.2:c.-452C>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
  • NM_000535.7:c.433C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322003.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322004.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322005.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.433C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322007.2:c.115C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322008.2:c.115C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322009.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322010.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322013.2:c.28C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.433C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322015.2:c.124C>A - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.520C>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]


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)
SCV000218761Invitaecriteria provided, single submitter
Uncertain significance
(Dec 19, 2019)
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



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]

Details of each submission

From Invitae, SCV000218761.8

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


This sequence change replaces glutamine with lysine at codon 145 of the PMS2 protein (p.Gln145Lys). The glutamine residue is moderately conserved and there is a small physicochemical difference between glutamine and lysine. 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 disease. ClinVar contains an entry for this variant (Variation ID: 188191). Algorithms developed to predict the effect of missense changes on protein structure and function (SIFT, PolyPhen-2, Align-GVGD) all suggest that this variant is likely to be tolerated, but these predictions have not been confirmed by published functional studies and their clinical significance is uncertain. In summary, the available evidence is currently insufficient to determine the role of this variant in disease. Therefore, it has been classified as a Variant of Uncertain Significance.

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

Last Updated: Dec 4, 2021

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