NM_000535.7(PMS2):c.1688_1689delinsAG (p.Arg563Gln) AND not specified

Clinical significance:Likely benign (Last evaluated: Oct 15, 2020)

Review status:1 star out of maximum of 4 stars

criteria provided, single submitter

Based on:
1 submission [Details]
Record status:
current
Accession:
RCV001263509.1

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

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

Gene:
PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]
Variant type:
Indel
Cytogenetic location:
7p22.1
Genomic location:
Preferred name:
NM_000535.7(PMS2):c.1688_1689delinsAG (p.Arg563Gln)
HGVS:
  • 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:
R252Q
Links:
dbSNP: rs587780725
NCBI 1000 Genomes Browser:
rs587780725
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]

Condition(s)

Synonyms:
AllHighlyPenetrant
Identifiers:
MedGen: CN169374

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Assertion and evidence details

Submission AccessionSubmitterReview Status
(Assertion method)
Clinical Significance
(Last evaluated)
OriginMethodCitations
SCV000697307Women's Health and Genetics/Laboratory Corporation of America, LabCorpcriteria provided, single submitter
Likely benign
(Oct 15, 2020)
germlineclinical testing

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

Citation Link

Summary from all submissions

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

Citations

PubMed

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]
PMID:
30093976
PMCID:
PMC6078133

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV000697307.2

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

Description

Variant summary: PMS2 c.1688_1689delinsAG (p.Arg563Gln) results in a conservative amino acid change in the encoded protein sequence. Three of five in-silico tools predict a benign effect of the variant on protein function. The variant allele was found at a frequency of 0.00023 in 276964 control chromosomes. The observed variant frequency is approximately 3 fold of the estimated maximal expected allele frequency for a pathogenic variant in PMS2 causing Hereditary Nonpolyposis Colorectal Cancer phenotype (7.1e-05), strongly suggesting that the variant is benign. c.1688_1689delinsAG has been reported in the literature in one individual affected with Breast Cancer (Chan_2018). This report does not provide unequivocal conclusions about association of the variant with Hereditary Nonpolyposis Colorectal Cancer. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Four clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. Multiple laboratories reported the variant with conflicting assessments (likely benign n=2, VUS n=2). Based on the evidence outlined above, the variant was classified as likely benign.

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

Last Updated: Jun 23, 2021

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