NM_000535.7(PMS2):c.2186_2187del (p.Leu729fs) AND Hereditary nonpolyposis colorectal neoplasms

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Aug 21, 2019
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:: RCV000544078.5

Allele description [Variation Report for NM_000535.7(PMS2):c.2186_2187del (p.Leu729fs)]

NM_000535.7(PMS2):c.2186_2187del (p.Leu729fs)

Gene:

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

Variant type:

Microsatellite

Cytogenetic location:

7p22.1

Genomic location:

Preferred name:

NM_000535.7(PMS2):c.2186_2187del (p.Leu729fs)

HGVS:

NC_000007.14:g.5978685AG[1]
NG_008466.1:g.35420TC[1]
NM_000535.7:c.2186_2187delMANE SELECT
NM_001322003.2:c.1781_1782del
NM_001322004.2:c.1781_1782del
NM_001322005.2:c.1781_1782del
NM_001322006.2:c.2030_2031del
NM_001322007.2:c.1868_1869del
NM_001322008.2:c.1868_1869del
NM_001322009.2:c.1781_1782del
NM_001322010.2:c.1625_1626del
NM_001322011.2:c.1253_1254del
NM_001322012.2:c.1253_1254del
NM_001322013.2:c.1613_1614del
NM_001322014.2:c.2186_2187del
NM_001322015.2:c.1877_1878del
NP_000526.2:p.Leu729fs
NP_001308932.1:p.Leu594fs
NP_001308933.1:p.Leu594fs
NP_001308934.1:p.Leu594fs
NP_001308935.1:p.Leu677fs
NP_001308936.1:p.Leu623fs
NP_001308937.1:p.Leu623fs
NP_001308938.1:p.Leu594fs
NP_001308939.1:p.Leu542fs
NP_001308940.1:p.Leu418fs
NP_001308941.1:p.Leu418fs
NP_001308942.1:p.Leu538fs
NP_001308943.1:p.Leu729fs
NP_001308944.1:p.Leu626fs
LRG_161t1:c.2186_2187del
LRG_161:g.35420TC[1]
NC_000007.13:g.6018315_6018316delGA
NC_000007.13:g.6018316AG[1]
NM_000535.5:c.2186_2187delTC
NM_000535.6:c.2186_2187del
NM_000535.6:c.2186_2187delTC
NM_000535.7:c.2186_2187delTCMANE SELECT
NM_001322014.2:c.2186_2187delTC
NR_136154.1:n.2271TC[1]

Protein change:

L418fs

Links:

OMIM: 600259.0005; dbSNP: rs587779335

NCBI 1000 Genomes Browser:

rs587779335

Molecular consequence:

NM_000535.7:c.2186_2187del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322003.2:c.1781_1782del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322004.2:c.1781_1782del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322005.2:c.1781_1782del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322006.2:c.2030_2031del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322007.2:c.1868_1869del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322008.2:c.1868_1869del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322009.2:c.1781_1782del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322010.2:c.1625_1626del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322011.2:c.1253_1254del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322012.2:c.1253_1254del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322013.2:c.1613_1614del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322014.2:c.2186_2187del - frameshift variant - [Sequence Ontology: SO:0001589]
NM_001322015.2:c.1877_1878del - frameshift variant - [Sequence Ontology: SO:0001589]
NR_136154.1:n.2271TC[1] - non-coding transcript variant - [Sequence Ontology: SO:0001619]

Condition(s)

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

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV000625597	Labcorp Genetics (formerly Invitae), Labcorp	criteria provided, single submitter (Invitae Variant Classification Sherloc (09022015))	Pathogenic (Aug 21, 2019)	germline	clinical testing	PubMed (3) [See all records that cite these PMIDs] 15077197, 24556621, 28492532

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV000625597

Labcorp Genetics (formerly Invitae), Labcorp

criteria provided, single submitter

(Invitae Variant Classification Sherloc (09022015))

Pathogenic
(Aug 21, 2019)

germline

clinical testing

PubMed (3)
[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

Novel PMS2 pseudogenes can conceal recessive mutations causing a distinctive childhood cancer syndrome.

De Vos M, Hayward BE, Picton S, Sheridan E, Bonthron DT.

Am J Hum Genet. 2004 May;74(5):954-64. Epub 2004 Apr 7.

PubMed [citation]

PMID:: 15077197
PMCID:: PMC1181988

Frequent germline deleterious mutations in DNA repair genes in familial prostate cancer cases are associated with advanced disease.

Leongamornlert D, Saunders E, Dadaev T, Tymrakiewicz M, Goh C, Jugurnauth-Little S, Kozarewa I, Fenwick K, Assiotis I, Barrowdale D, Govindasami K, Guy M, Sawyer E, Wilkinson R; UKGPCS Collaborators, Antoniou AC, Eeles R, Kote-Jarai Z.

Br J Cancer. 2014 Mar 18;110(6):1663-72. doi: 10.1038/bjc.2014.30. Epub 2014 Feb 20.

PubMed [citation]

PMID:: 24556621
PMCID:: PMC3960610

See all PubMed Citations (3)

Details of each submission

From Labcorp Genetics (formerly Invitae), Labcorp, SCV000625597.3

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (3)

Description

This sequence change creates a premature translational stop signal (p.Leu729Glnfs*6) in the PMS2 gene. It is expected to result in an absent or disrupted protein product. The frequency data for this variant in the population databases (ExAC) is considered unreliable due to the presence of homologous sequence, such as pseudogenes or paralogs, in the genome. This variant has been observed in several individuals affected prostate cancer and constitutional mismatch repair deficiency syndrome (PMID: 24556621, 15077197). This variant is also known as c.2184delTC in the literature. Loss-of-function variants in PMS2 are known to be pathogenic (PMID: 21376568, 24362816). For these reasons, this variant has been classified as 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: Dec 22, 2024

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