NM_000535.7(PMS2):c.497T>C (p.Leu166Pro) AND not provided

Germline classification:: Conflicting interpretations of pathogenicity (3 submissions)
Last evaluated:: Aug 9, 2023
Review status:: criteria provided, conflicting classifications

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:: RCV000587642.21

Allele description [Variation Report for NM_000535.7(PMS2):c.497T>C (p.Leu166Pro)]

NM_000535.7(PMS2):c.497T>C (p.Leu166Pro)

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.497T>C (p.Leu166Pro)

Other names:

p.L166P:CTA>CCA

HGVS:

NC_000007.14:g.6002493A>G
NG_008466.1:g.11614T>C
NM_000535.7:c.497T>CMANE SELECT
NM_001322003.2:c.92T>C
NM_001322004.2:c.92T>C
NM_001322005.2:c.92T>C
NM_001322006.2:c.497T>C
NM_001322007.2:c.179T>C
NM_001322008.2:c.179T>C
NM_001322009.2:c.92T>C
NM_001322010.2:c.92T>C
NM_001322011.2:c.-388T>C
NM_001322012.2:c.-388T>C
NM_001322013.2:c.92T>C
NM_001322014.2:c.497T>C
NM_001322015.2:c.188T>C
NP_000526.2:p.Leu166Pro
NP_001308932.1:p.Leu31Pro
NP_001308933.1:p.Leu31Pro
NP_001308934.1:p.Leu31Pro
NP_001308935.1:p.Leu166Pro
NP_001308936.1:p.Leu60Pro
NP_001308937.1:p.Leu60Pro
NP_001308938.1:p.Leu31Pro
NP_001308939.1:p.Leu31Pro
NP_001308942.1:p.Leu31Pro
NP_001308943.1:p.Leu166Pro
NP_001308944.1:p.Leu63Pro
LRG_161t1:c.497T>C
LRG_161:g.11614T>C
NC_000007.13:g.6042124A>G
NM_000535.5:c.497T>C
NM_000535.6:c.497T>C
NR_136154.1:n.584T>C
p.L166P

Protein change:

L166P

Links:

dbSNP: rs116349687

NCBI 1000 Genomes Browser:

rs116349687

Molecular consequence:

NM_001322011.2:c.-388T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-388T>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_000535.7:c.497T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.92T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.92T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.92T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.497T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.179T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.179T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.92T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.92T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322013.2:c.92T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.497T>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.188T>C - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.584T>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Observations:

Condition(s)

Synonyms:: none provided
Identifiers:: MedGen: C3661900

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000211590	GeneDx	criteria provided, single submitter (GeneDx Variant Classification Process June 2021)	Uncertain significance (Mar 29, 2021)	germline	clinical testing	Citation Link,
SCV000601851	Quest Diagnostics Nichols Institute San Juan Capistrano	criteria provided, single submitter (Quest Diagnostics criteria)	Likely benign (Aug 9, 2023)	unknown	clinical testing	PubMed (7) [See all records that cite these PMIDs] 35264596, 28135145, 29356034, 24113346, 27443514, 25980754, 26467025
SCV000860664	Eurofins Ntd Llc (ga)	criteria provided, single submitter (EGL ClinVar v180209 classification definitions)	Uncertain significance (Apr 5, 2018)	germline	clinical testing	Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000211590

GeneDx

criteria provided, single submitter

(GeneDx Variant Classification Process June 2021)

Uncertain significance
(Mar 29, 2021)

germline

clinical testing

Citation Link,

SCV000601851

Quest Diagnostics Nichols Institute San Juan Capistrano

criteria provided, single submitter

(Quest Diagnostics criteria)

Likely benign
(Aug 9, 2023)

unknown

clinical testing

PubMed (7)
[See all records that cite these PMIDs]

SCV000860664

Eurofins Ntd Llc (ga)

criteria provided, single submitter

(EGL ClinVar v180209 classification definitions)

Uncertain significance
(Apr 5, 2018)

germline

clinical testing

Citation Link

Help

Summary from all submissions

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

Citations

PubMed

Detection of germline variants in Brazilian breast cancer patients using multigene panel testing.

Guindalini RSC, Viana DV, Kitajima JPFW, Rocha VM, López RVM, Zheng Y, Freitas É, Monteiro FPM, Valim A, Schlesinger D, Kok F, Olopade OI, Folgueira MAAK.

Sci Rep. 2022 Mar 9;12(1):4190. doi: 10.1038/s41598-022-07383-1.

PubMed [citation]

PMID:: 35264596
PMCID:: PMC8907244

Cancer Susceptibility Gene Mutations in Individuals With Colorectal Cancer.

Yurgelun MB, Kulke MH, Fuchs CS, Allen BA, Uno H, Hornick JL, Ukaegbu CI, Brais LK, McNamara PG, Mayer RJ, Schrag D, Meyerhardt JA, Ng K, Kidd J, Singh N, Hartman AR, Wenstrup RJ, Syngal S.

J Clin Oncol. 2017 Apr 1;35(10):1086-1095. doi: 10.1200/JCO.2016.71.0012. Epub 2017 Jan 30.

PubMed [citation]

PMID:: 28135145
PMCID:: PMC5455355

See all PubMed Citations (7)

Details of each submission

From GeneDx, SCV000211590.12

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

Description

In silico analysis supports that this missense variant has a deleterious effect on protein structure/function; Observed in individuals with endometrial cancer, colorectal cancer, or prostate cancer, with a colon tumor from at least one individual showing loss of MLH1 and PMS2 proteins on immunohistochemistry (Ring 2016, Yurgelun 2017, Beebe-Dimmer 2018); This variant is associated with the following publications: (PMID: 29356034, 27443514, 24113346, 28135145, 25980754)

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

From Quest Diagnostics Nichols Institute San Juan Capistrano, SCV000601851.4

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (7)

#	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 Eurofins Ntd Llc (ga), SCV000860664.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	1	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	germline	unknown	not provided	not provided	not provided		1	not provided	not provided	not provided

Last Updated: Oct 13, 2024

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