NM_000535.7(PMS2):c.632G>A (p.Arg211Gln) AND Lynch syndrome

Germline classification:: Uncertain significance (1 submission)
Last evaluated:: Jan 11, 2024
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:: RCV003998053.2

Allele description [Variation Report for NM_000535.7(PMS2):c.632G>A (p.Arg211Gln)]

NM_000535.7(PMS2):c.632G>A (p.Arg211Gln)

Gene:

PMS2:PMS1 homolog 2, mismatch repair system component [Gene - OMIM - HGNC]

Variant type:

single nucleotide variant

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_000535.7(PMS2):c.632G>A (p.Arg211Gln)

Other names:

p.R211Q:CGA>CAA

HGVS:

NC_000007.14:g.5999181C>T
NG_008466.1:g.14926G>A
NM_000535.7:c.632G>AMANE SELECT
NM_001322003.2:c.227G>A
NM_001322004.2:c.227G>A
NM_001322005.2:c.227G>A
NM_001322006.2:c.632G>A
NM_001322007.2:c.314G>A
NM_001322008.2:c.314G>A
NM_001322009.2:c.227G>A
NM_001322010.2:c.227G>A
NM_001322011.2:c.-302G>A
NM_001322012.2:c.-302G>A
NM_001322013.2:c.133-1758G>A
NM_001322014.2:c.632G>A
NM_001322015.2:c.323G>A
NP_000526.2:p.Arg211Gln
NP_001308932.1:p.Arg76Gln
NP_001308933.1:p.Arg76Gln
NP_001308934.1:p.Arg76Gln
NP_001308935.1:p.Arg211Gln
NP_001308936.1:p.Arg105Gln
NP_001308937.1:p.Arg105Gln
NP_001308938.1:p.Arg76Gln
NP_001308939.1:p.Arg76Gln
NP_001308943.1:p.Arg211Gln
NP_001308944.1:p.Arg108Gln
LRG_161t1:c.632G>A
LRG_161:g.14926G>A
NC_000007.13:g.6038812C>T
NM_000535.5:c.632G>A
NM_000535.6:c.632G>A
NR_136154.1:n.719G>A
p.R211Q

Protein change:

R105Q

Links:

dbSNP: rs587781934

NCBI 1000 Genomes Browser:

rs587781934

Molecular consequence:

NM_001322011.2:c.-302G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-302G>A - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.133-1758G>A - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.632G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.227G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.227G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.227G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.632G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.314G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.314G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.227G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.227G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.632G>A - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.323G>A - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.719G>A - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Name:: Lynch syndrome
Identifiers:: MONDO: MONDO:0005835; MedGen: C4552100

Recent activity

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lipase member N isoform X2 [Homo sapiens]
lipase member N isoform X2 [Homo sapiens]
gi|2217278352|ref|XP_047281599.1|

Protein
PREDICTED: Homo sapiens lipase family member N (LIPN), transcript variant X2, mR...
PREDICTED: Homo sapiens lipase family member N (LIPN), transcript variant X2, mRNA
gi|2217278348|ref|XM_047425642.1|

Nucleotide

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV004839946	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Jan 11, 2024)	germline	clinical testing	PubMed (8) [See all records that cite these PMIDs] 27616075, 31433215, 31992580, 32628757, 32885271, 33471991, 34359559, 25741868

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV004839946

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Jan 11, 2024)

germline

clinical testing

PubMed (8)
[See all records that cite these PMIDs]

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	17	not provided	not provided	108544	not provided	clinical testing

Citations

PubMed

Gene panel sequencing in familial breast/ovarian cancer patients identifies multiple novel mutations also in genes others than BRCA1/2.

Kraus C, Hoyer J, Vasileiou G, Wunderle M, Lux MP, Fasching PA, Krumbiegel M, Uebe S, Reuter M, Beckmann MW, Reis A.

Int J Cancer. 2017 Jan 1;140(1):95-102. doi: 10.1002/ijc.30428. Epub 2016 Sep 23.

PubMed [citation]

PMID:: 27616075

Detection of PMS2 Mutations by Screening Hereditary Nonpolyposis Colon Cancer Families from Denmark and Sweden.

Okkels H, Lagerstedt-Robinsson K, Wikman FP, Hansen TVO, Lolas I, Lindberg LJ, Krarup HB.

Genet Test Mol Biomarkers. 2019 Sep;23(9):688-695. doi: 10.1089/gtmb.2018.0316. Epub 2019 Aug 21.

PubMed [citation]

PMID:: 31433215

See all PubMed Citations (8)

Details of each submission

From All of Us Research Program, National Institutes of Health, SCV004839946.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	17	not provided	not provided	clinical testing	PubMed (8)

Description

This missense variant replaces arginine with glutamine at codon 211 of the PMS2 protein. Computational prediction suggests that this variant may not impact protein structure and function (internally defined REVEL score threshold <= 0.5, PMID: 27666373). To our knowledge, functional studies have not been reported for this variant. This variant has been reported in individuals affected with Lynch syndrome and ovarian cancer (PMID: 27616075, 31433215, 31992580, 32628757). This variant has also been reported in individuals affected with breast cancer (PMID: 32885271, 33471991, 34359559), as well as ten healthy controls in a breast cancer case-control study (PMID: 33471991). This variant has been identified in 12/282866 chromosomes in the general population by the Genome Aggregation Database (gnomAD). The available evidence is insufficient to determine the role of this variant in disease conclusively. Therefore, this variant is classified as a Variant of Uncertain Significance.

#	Sample				Method		Observation
#	Origin	Affected	Number tested	Tissue	Purpose	Method	Individuals	Allele frequency	Families	Co-occurrences
1	germline	unknown	108544	not provided	not provided		17	not provided	not provided	not provided

Last Updated: Oct 20, 2024

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