NM_000535.7(PMS2):c.88C>T (p.Gln30Ter) AND Hereditary nonpolyposis colon cancer

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Mar 6, 2020
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:: RCV001175479.1

Allele description [Variation Report for NM_000535.7(PMS2):c.88C>T (p.Gln30Ter)]

NM_000535.7(PMS2):c.88C>T (p.Gln30Ter)

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.88C>T (p.Gln30Ter)

HGVS:

NC_000007.14:g.6005967G>A
NG_008466.1:g.8140C>T
NG_050738.1:g.1717G>A
NM_000535.7:c.88C>TMANE SELECT
NM_001322003.2:c.-318C>T
NM_001322004.2:c.-242-1909C>T
NM_001322005.2:c.-318C>T
NM_001322006.2:c.88C>T
NM_001322007.2:c.-128C>T
NM_001322008.2:c.-52-1909C>T
NM_001322009.2:c.-318C>T
NM_001322010.2:c.-242-1909C>T
NM_001322011.2:c.-797C>T
NM_001322012.2:c.-797C>T
NM_001322013.2:c.-318C>T
NM_001322014.2:c.88C>T
NM_001322015.2:c.-397C>T
NP_000526.2:p.Gln30Ter
NP_001308935.1:p.Gln30Ter
NP_001308943.1:p.Gln30Ter
LRG_161t1:c.88C>T
LRG_161:g.8140C>T
NC_000007.13:g.6045598G>A
NM_000535.5:c.88C>T
NM_000535.6:c.88C>T
NR_136154.1:n.175C>T
p.Gln30X
p.Q30*

Protein change:

Q30*

Links:

dbSNP: rs141577476

NCBI 1000 Genomes Browser:

rs141577476

Molecular consequence:

NM_001322003.2:c.-318C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322005.2:c.-318C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322007.2:c.-128C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322009.2:c.-318C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322011.2:c.-797C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-797C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322013.2:c.-318C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322015.2:c.-397C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322004.2:c.-242-1909C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001322008.2:c.-52-1909C>T - intron variant - [Sequence Ontology: SO:0001627]
NM_001322010.2:c.-242-1909C>T - intron variant - [Sequence Ontology: SO:0001627]
NR_136154.1:n.175C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000535.7:c.88C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322006.2:c.88C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322014.2:c.88C>T - nonsense - [Sequence Ontology: SO:0001587]

Condition(s)

Name:: Hereditary nonpolyposis colon cancer (HNPCC)
Synonyms:: Hereditary nonpolyposis colorectal cancer; Familial nonpolyposis colon cancer; Hereditary Nonpolyposis Colorectal Cancer Syndrome
Identifiers:: MONDO: MONDO:0018630; MedGen: C1333990; OMIM: PS120435

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Submission Accession	Submitter	Review Status (Assertion method)	Clinical Significance (Last evaluated)	Origin	Method	Citations
SCV001339068	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Mar 6, 2020)	germline	clinical testing	PubMed (2) [See all records that cite these PMIDs] 25856668, 28152038 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001339068

Women's Health and Genetics/Laboratory Corporation of America, LabCorp

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Mar 6, 2020)

germline

clinical testing

PubMed (2)
[See all records that cite these PMIDs]

Citation Link

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

PMS2 monoallelic mutation carriers: the known unknown.

Goodenberger ML, Thomas BC, Riegert-Johnson D, Boland CR, Plon SE, Clendenning M, Win AK, Senter L, Lipkin SM, Stadler ZK, Macrae FA, Lynch HT, Weitzel JN, de la Chapelle A, Syngal S, Lynch P, Parry S, Jenkins MA, Gallinger S, Holter S, Aronson M, Newcomb PA, et al.

Genet Med. 2016 Jan;18(1):13-9. doi: 10.1038/gim.2015.27. Epub 2015 Apr 9. Review.

PubMed [citation]

PMID:: 25856668
PMCID:: PMC4834863

Exome sequencing covers >98% of mutations identified on targeted next generation sequencing panels.

LaDuca H, Farwell KD, Vuong H, Lu HM, Mu W, Shahmirzadi L, Tang S, Chen J, Bhide S, Chao EC.

PLoS One. 2017;12(2):e0170843. doi: 10.1371/journal.pone.0170843.

PubMed [citation]

PMID:: 28152038
PMCID:: PMC5289469

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001339068.1

#	Ethnicity	Individuals	Chromosomes Tested	Family History	Method	Citations
1	not provided	not provided	not provided	not provided	clinical testing	PubMed (2)

Description

Variant summary: PMS2 c.88C>T (p.Gln30X) results in a premature termination codon, predicted to cause a truncation of the encoded protein or absence of the protein due to nonsense mediated decay, which are commonly known mechanisms for disease. Truncations downstream of this position have been classified as pathogenic by our laboratory. The variant was absent in 245770 control chromosomes. c.88C>T has been reported in the literature in individuals affected with endometrial and/or ovarian cancer (Goodenberger_2015). To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Five clinical diagnostic laboratories have submitted clinical-significance assessments for this variant to ClinVar after 2014 without evidence for independent evaluation. All laboratories classified the variant as pathogenic. Based on the evidence outlined above, the variant was 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: Sep 29, 2024

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