NM_000535.7(PMS2):c.614A>C (p.Gln205Pro) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Likely pathogenic (1 submission)
Last evaluated:: Jan 14, 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:: RCV000524477.10

Allele description [Variation Report for NM_000535.7(PMS2):c.614A>C (p.Gln205Pro)]

NM_000535.7(PMS2):c.614A>C (p.Gln205Pro)

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.614A>C (p.Gln205Pro)

HGVS:

NC_000007.14:g.5999199T>G
NG_008466.1:g.14908A>C
NM_000535.7:c.614A>CMANE SELECT
NM_001322003.2:c.209A>C
NM_001322004.2:c.209A>C
NM_001322005.2:c.209A>C
NM_001322006.2:c.614A>C
NM_001322007.2:c.296A>C
NM_001322008.2:c.296A>C
NM_001322009.2:c.209A>C
NM_001322010.2:c.209A>C
NM_001322011.2:c.-320A>C
NM_001322012.2:c.-320A>C
NM_001322013.2:c.133-1776A>C
NM_001322014.2:c.614A>C
NM_001322015.2:c.305A>C
NP_000526.2:p.Gln205Pro
NP_001308932.1:p.Gln70Pro
NP_001308933.1:p.Gln70Pro
NP_001308934.1:p.Gln70Pro
NP_001308935.1:p.Gln205Pro
NP_001308936.1:p.Gln99Pro
NP_001308937.1:p.Gln99Pro
NP_001308938.1:p.Gln70Pro
NP_001308939.1:p.Gln70Pro
NP_001308943.1:p.Gln205Pro
NP_001308944.1:p.Gln102Pro
LRG_161t1:c.614A>C
LRG_161:g.14908A>C
NC_000007.13:g.6038830T>G
NM_000535.5:c.614A>C
NM_000535.6:c.614A>C
NR_136154.1:n.701A>C
p.Q205P

Protein change:

Q102P

Links:

dbSNP: rs587779342

NCBI 1000 Genomes Browser:

rs587779342

Molecular consequence:

NM_001322011.2:c.-320A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-320A>C - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.133-1776A>C - intron variant - [Sequence Ontology: SO:0001627]
NM_000535.7:c.614A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322003.2:c.209A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322004.2:c.209A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322005.2:c.209A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322006.2:c.614A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322007.2:c.296A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322008.2:c.296A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322009.2:c.209A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322010.2:c.209A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322014.2:c.614A>C - missense variant - [Sequence Ontology: SO:0001583]
NM_001322015.2:c.305A>C - missense variant - [Sequence Ontology: SO:0001583]
NR_136154.1:n.701A>C - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

Name:: Hereditary nonpolyposis colorectal neoplasms
Identifiers:: MeSH: D003123; MedGen: C0009405

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homo sapiens[Organism] AND MIR4697 AND (alive[prop]) (5)
Gene
hypothetical protein E6C27_scaffold65G005880 [Cucumis melo var. makuwa]
hypothetical protein E6C27_scaffold65G005880 [Cucumis melo var. makuwa]
gi|1735191840|gb|KAA0034572.1||gnl| STE|E6C27_scaffold65G005880

Protein

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000285143	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Likely pathogenic (Jan 14, 2024)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 18602922, 25980754, 27435373, 2402700, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000285143

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Likely pathogenic
(Jan 14, 2024)

germline

clinical testing

PubMed (5)
[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	not provided	not provided	not provided	not provided	not provided	clinical testing

Citations

PubMed

The clinical phenotype of Lynch syndrome due to germ-line PMS2 mutations.

Senter L, Clendenning M, Sotamaa K, Hampel H, Green J, Potter JD, Lindblom A, Lagerstedt K, Thibodeau SN, Lindor NM, Young J, Winship I, Dowty JG, White DM, Hopper JL, Baglietto L, Jenkins MA, de la Chapelle A.

Gastroenterology. 2008 Aug;135(2):419-28. doi: 10.1053/j.gastro.2008.04.026. Epub 2008 May 2.

PubMed [citation]

PMID:: 18602922
PMCID:: PMC2759321

Identification of a Variety of Mutations in Cancer Predisposition Genes in Patients With Suspected Lynch Syndrome.

Yurgelun MB, Allen B, Kaldate RR, Bowles KR, Judkins T, Kaushik P, Roa BB, Wenstrup RJ, Hartman AR, Syngal S.

Gastroenterology. 2015 Sep;149(3):604-13.e20. doi: 10.1053/j.gastro.2015.05.006. Epub 2015 May 14.

PubMed [citation]

PMID:: 25980754
PMCID:: PMC4550537

See all PubMed Citations (5)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000285143.11

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (5)

Description

This sequence change replaces glutamine, which is neutral and polar, with proline, which is neutral and non-polar, at codon 205 of the PMS2 protein (p.Gln205Pro). This variant is present in population databases (rs587779342, gnomAD 0.0009%). This missense change has been observed in individual(s) with constitutional mismatch repair deficiency and clinical features of Lynch syndrome (PMID: 18602922, 25980754, 27435373). ClinVar contains an entry for this variant (Variation ID: 91361). Advanced modeling of protein sequence and biophysical properties (such as structural, functional, and spatial information, amino acid conservation, physicochemical variation, residue mobility, and thermodynamic stability) performed at Invitae indicates that this missense variant is expected to disrupt PMS2 protein function with a positive predictive value of 80%. Experimental studies have shown that this missense change affects PMS2 function (PMID: 2402700). In summary, the currently available evidence indicates that the variant is pathogenic, but additional data are needed to prove that conclusively. Therefore, this variant has been classified as Likely Pathogenic.

#	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: Oct 8, 2024

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