NM_000535.7(PMS2):c.1688_1689delinsAG (p.Arg563Gln) AND Hereditary cancer-predisposing syndrome

Clinical significance:Conflicting interpretations of pathogenicity, Likely benign(1);Uncertain significance(1) (Last evaluated: Jul 7, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, conflicting interpretations

Based on:
2 submissions [Details]
Record status:

Allele description [Variation Report for NM_000535.7(PMS2):c.1688_1689delinsAG (p.Arg563Gln)]

NM_000535.7(PMS2):c.1688_1689delinsAG (p.Arg563Gln)

PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
Cytogenetic location:
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.1688_1689delinsAG (p.Arg563Gln)
  • NC_000007.14:g.5987076_5987077delinsCT
  • NG_008466.1:g.27030_27031delinsAG
  • NM_000535.7:c.1688_1689delinsAGMANE SELECT
  • NM_001322003.2:c.1283_1284delinsAG
  • NM_001322004.2:c.1283_1284delinsAG
  • NM_001322005.2:c.1283_1284delinsAG
  • NM_001322006.2:c.1532_1533delinsAG
  • NM_001322007.1:c.1370_1371delinsAG
  • NM_001322008.2:c.1370_1371delinsAG
  • NM_001322009.2:c.1283_1284delinsAG
  • NM_001322010.2:c.1127_1128delinsAG
  • NM_001322011.2:c.755_756delinsAG
  • NM_001322012.2:c.755_756delinsAG
  • NM_001322013.2:c.1115_1116delinsAG
  • NM_001322014.2:c.1688_1689delinsAG
  • NM_001322015.2:c.1379_1380delinsAG
  • NP_000526.2:p.Arg563Gln
  • NP_001308932.1:p.Arg428Gln
  • NP_001308933.1:p.Arg428Gln
  • NP_001308934.1:p.Arg428Gln
  • NP_001308935.1:p.Arg511Gln
  • NP_001308936.1:p.Arg457Gln
  • NP_001308937.1:p.Arg457Gln
  • NP_001308938.1:p.Arg428Gln
  • NP_001308939.1:p.Arg376Gln
  • NP_001308940.1:p.Arg252Gln
  • NP_001308941.1:p.Arg252Gln
  • NP_001308942.1:p.Arg372Gln
  • NP_001308943.1:p.Arg563Gln
  • NP_001308944.1:p.Arg460Gln
  • LRG_161t1:c.1688_1689delGAinsAG
  • LRG_161:g.27030_27031delinsAG
  • NC_000007.13:g.6026707_6026708delinsCT
  • NM_000535.5:c.1688_1689delGAinsAG
  • NM_000535.6:c.1688_1689delGAinsAG
  • NR_136154.1:n.1775_1776delinsAG
  • p.R563Q
Protein change:
dbSNP: rs587780725
NCBI 1000 Genomes Browser:
Molecular consequence:
  • NM_000535.7:c.1688_1689delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322003.2:c.1283_1284delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322004.2:c.1283_1284delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322005.2:c.1283_1284delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322006.2:c.1532_1533delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322007.1:c.1370_1371delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322008.2:c.1370_1371delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322009.2:c.1283_1284delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322010.2:c.1127_1128delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322011.2:c.755_756delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322012.2:c.755_756delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322013.2:c.1115_1116delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322014.2:c.1688_1689delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NM_001322015.2:c.1379_1380delinsAG - missense variant - [Sequence Ontology: SO:0001583]
  • NR_136154.1:n.1775_1776delinsAG - non-coding transcript variant - [Sequence Ontology: SO:0001619]


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

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
SCV000187550Ambry Geneticscriteria provided, single submitter
Uncertain significance
(Jul 7, 2020)
germlineclinical testing

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

Citation Link,

SCV000902632Color Health, Inccriteria provided, single submitter
Likely benign
(Jul 14, 2016)
germlineclinical testing

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

Summary from all submissions

EthnicityOriginAffectedIndividualsFamiliesChromosomes testedNumber TestedFamily historyMethod
not providedgermlineunknown1not providednot provided1not providedclinical testing



Clinical genetic testing outcome with multi-gene panel in Asian patients with multiple primary cancers.

Chan GHJ, Ong PY, Low JJH, Kong HL, Ow SGW, Tan DSP, Lim YW, Lim SE, Lee SC.

Oncotarget. 2018 Jul 17;9(55):30649-30660. doi: 10.18632/oncotarget.25769.

PubMed [citation]

Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology.

Richards S, Aziz N, Bale S, Bick D, Das S, Gastier-Foster J, Grody WW, Hegde M, Lyon E, Spector E, Voelkerding K, Rehm HL; ACMG Laboratory Quality Assurance Committee..

Genet Med. 2015 May;17(5):405-24. doi: 10.1038/gim.2015.30. Epub 2015 Mar 5.

PubMed [citation]

Details of each submission

From Ambry Genetics, SCV000187550.6

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


The c.1688_1689delGAinsAG variant (also known as p.R563Q), located in coding exon 11 of the PMS2 gene, results from an in-frame deletion of GA and insertion of AG at nucleotide positions 1688 to 1689. The arginine at codon 563 is replaced by glutamine, an amino acid with highly similar properties. This alteration has been reported in an Asian individual with a personal history of breast cancer (Chan GHJ et al. Oncotarget. 2018 Jul;9:30649-30660). This amino acid position is not well conserved in available vertebrate species. In addition, this alteration is predicted to be neutral<span style="color:rgb(255, 0, 0)"> by in silico analysis (Choi Y et al. PLoS ONE. 2012; 7(10):e46688). Since supporting evidence is limited at this time, the clinical significance of this alteration remains unclear.

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

From Color Health, Inc, SCV000902632.1

#EthnicityIndividualsChromosomes TestedFamily HistoryMethodCitations
1not providednot providednot providednot providedclinical testing PubMed (1)
OriginAffectedNumber testedTissuePurposeMethodIndividualsAllele frequencyFamiliesCo-occurrences
1germlineunknownnot providednot providednot providednot providednot providednot providednot provided

Last Updated: Jun 23, 2021

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