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

Germline classification:: Likely benign (1 submission)
Last evaluated:: Jan 6, 2023
Review status:: 1 star out of maximum of 4 stars
criteria provided, single submitter

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:: RCV001263509.4

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_001322007.2: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_001322007.2: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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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000697307	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Likely benign (Jan 6, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID] Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000697307

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Likely benign
(Jan 6, 2023)

germline

clinical testing

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

Citation Link

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	not provided	not provided	not provided	not provided	not provided	clinical 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, SCV000697307.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical 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=3, VUS n=1). Based on the evidence outlined above, the variant was classified as likely benign.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	not provided	not provided	not provided		not provided	not provided	not provided	not provided

Last Updated: Apr 15, 2024

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