NM_000535.7(PMS2):c.1511A>G (p.Glu504Gly) AND Lynch syndrome

Germline classification:: Uncertain significance (2 submissions)
Last evaluated:: Dec 1, 2023
Review status:: 2 stars out of maximum of 4 stars
criteria provided, multiple submitters, no conflicts

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:: RCV000708982.3

Allele description [Variation Report for NM_000535.7(PMS2):c.1511A>G (p.Glu504Gly)]

NM_000535.7(PMS2):c.1511A>G (p.Glu504Gly)

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.1511A>G (p.Glu504Gly)

HGVS:

NC_000007.14:g.5987254T>C
NG_008466.1:g.26853A>G
NM_000535.7:c.1511A>GMANE SELECT
NM_001322003.2:c.1106A>G
NM_001322004.2:c.1106A>G
NM_001322005.2:c.1106A>G
NM_001322006.2:c.1355A>G
NM_001322007.2:c.1193A>G
NM_001322008.2:c.1193A>G
NM_001322009.2:c.1106A>G
NM_001322010.2:c.950A>G
NM_001322011.2:c.578A>G
NM_001322012.2:c.578A>G
NM_001322013.2:c.938A>G
NM_001322014.2:c.1511A>G
NM_001322015.2:c.1202A>G
NP_000526.2:p.Glu504Gly
NP_001308932.1:p.Glu369Gly
NP_001308933.1:p.Glu369Gly
NP_001308934.1:p.Glu369Gly
NP_001308935.1:p.Glu452Gly
NP_001308936.1:p.Glu398Gly
NP_001308937.1:p.Glu398Gly
NP_001308938.1:p.Glu369Gly
NP_001308939.1:p.Glu317Gly
NP_001308940.1:p.Glu193Gly
NP_001308941.1:p.Glu193Gly
NP_001308942.1:p.Glu313Gly
NP_001308943.1:p.Glu504Gly
NP_001308944.1:p.Glu401Gly
LRG_161t1:c.1511A>G
LRG_161:g.26853A>G
NC_000007.13:g.6026885T>C
NM_000535.5:c.1511A>G
NM_000535.6:c.1511A>G
NR_136154.1:n.1598A>G

Protein change:

E193G

Links:

dbSNP: rs1254121331

NCBI 1000 Genomes Browser:

rs1254121331

Molecular consequence:

NM_000535.7:c.1511A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.1106A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.1106A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.1106A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.1355A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.1193A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.1193A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.1106A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.950A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322011.2:c.578A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322012.2:c.578A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.938A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.1511A>G - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.1202A>G - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.1598A>G - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000838177	Mendelics	criteria provided, single submitter (Mendelics Assertion Criteria 2017)	Uncertain significance (Jul 2, 2018)	unknown	clinical testing	Citation Link,
SCV004844195	All of Us Research Program, National Institutes of Health	criteria provided, single submitter (ACMG Guidelines, 2015)	Uncertain Significance (Dec 1, 2023)	germline	clinical testing	PubMed (1) [See all records that cite this PMID]

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000838177

Mendelics

criteria provided, single submitter

(Mendelics Assertion Criteria 2017)

Uncertain significance
(Jul 2, 2018)

unknown

clinical testing

Citation Link,

SCV004844195

All of Us Research Program, National Institutes of Health

criteria provided, single submitter

(ACMG Guidelines, 2015)

Uncertain Significance
(Dec 1, 2023)

germline

clinical testing

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

Help

Summary from all submissions

Ethnicity	Origin	Affected	Individuals	Families	Chromosomes tested	Number Tested	Family history	Method
not provided	germline	unknown	1	not provided	not provided	108544	not provided	clinical testing
not provided	unknown	unknown	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

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]

PMID:: 25741868
PMCID:: PMC4544753

Details of each submission

From Mendelics, SCV000838177.2

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	not provided

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

From All of Us Research Program, National Institutes of Health, SCV004844195.1

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

Description

This missense variant replaces glutamic acid with glycine at codon 504 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 not been reported in individuals affected with hereditary cancer in the literature. This variant has been identified in 1/251394 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		1	not provided	not provided	not provided

Last Updated: Apr 20, 2024

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