NM_000535.7(PMS2):c.823C>T (p.Gln275Ter) AND Hereditary nonpolyposis colon cancer

Germline classification:: Pathogenic (1 submission)
Last evaluated:: Oct 28, 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:: RCV001264438.1

Allele description [Variation Report for NM_000535.7(PMS2):c.823C>T (p.Gln275Ter)]

NM_000535.7(PMS2):c.823C>T (p.Gln275Ter)

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.823C>T (p.Gln275Ter)

Other names:

p.Q275*:CAA>TAA

HGVS:

NC_000007.14:g.5995614G>A
NG_008466.1:g.18493C>T
NM_000535.7:c.823C>TMANE SELECT
NM_001322003.2:c.418C>T
NM_001322004.2:c.418C>T
NM_001322005.2:c.418C>T
NM_001322006.2:c.823C>T
NM_001322007.2:c.505C>T
NM_001322008.2:c.505C>T
NM_001322009.2:c.418C>T
NM_001322010.2:c.418C>T
NM_001322011.2:c.-111C>T
NM_001322012.2:c.-111C>T
NM_001322013.2:c.250C>T
NM_001322014.2:c.823C>T
NM_001322015.2:c.514C>T
NP_000526.2:p.Gln275Ter
NP_001308932.1:p.Gln140Ter
NP_001308933.1:p.Gln140Ter
NP_001308934.1:p.Gln140Ter
NP_001308935.1:p.Gln275Ter
NP_001308936.1:p.Gln169Ter
NP_001308937.1:p.Gln169Ter
NP_001308938.1:p.Gln140Ter
NP_001308939.1:p.Gln140Ter
NP_001308942.1:p.Gln84Ter
NP_001308943.1:p.Gln275Ter
NP_001308944.1:p.Gln172Ter
LRG_161t1:c.823C>T
LRG_161:g.18493C>T
NC_000007.13:g.6035245G>A
NM_000535.5:c.823C>T
NM_000535.6:c.823C>T
NR_136154.1:n.910C>T
p.Gln275Stop

Protein change:

Q140*

Links:

dbSNP: rs587780062

NCBI 1000 Genomes Browser:

rs587780062

Molecular consequence:

NM_001322011.2:c.-111C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NM_001322012.2:c.-111C>T - 5 prime UTR variant - [Sequence Ontology: SO:0001623]
NR_136154.1:n.910C>T - non-coding transcript variant - [Sequence Ontology: SO:0001619]
NM_000535.7:c.823C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322003.2:c.418C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322004.2:c.418C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322005.2:c.418C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322006.2:c.823C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322007.2:c.505C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322008.2:c.505C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322009.2:c.418C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322010.2:c.418C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322013.2:c.250C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322014.2:c.823C>T - nonsense - [Sequence Ontology: SO:0001587]
NM_001322015.2:c.514C>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
SCV001442589	Women's Health and Genetics/Laboratory Corporation of America, LabCorp	criteria provided, single submitter (LabCorp Variant Classification Summary - May 2015)	Pathogenic (Oct 28, 2020)	germline	clinical testing	PubMed (5) [See all records that cite these PMIDs] 24689082, 22848017, 27435373, 25512458, 31992580 Citation Link

Submission Accession

Submitter

Review Status
(Assertion method)

Clinical Significance
(Last evaluated)

Origin

Method

Citations

SCV001442589

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

criteria provided, single submitter

(LabCorp Variant Classification Summary - May 2015)

Pathogenic
(Oct 28, 2020)

germline

clinical testing

PubMed (5)
[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

A massive parallel sequencing workflow for diagnostic genetic testing of mismatch repair genes.

Hansen MF, Neckmann U, Lavik LA, Vold T, Gilde B, Toft RK, Sjursen W.

Mol Genet Genomic Med. 2014 Mar;2(2):186-200. doi: 10.1002/mgg3.62. Epub 2014 Jan 21.

PubMed [citation]

PMID:: 24689082
PMCID:: PMC3960061

Optic pathway glioma as part of a constitutional mismatch-repair deficiency syndrome in a patient meeting the criteria for neurofibromatosis type 1.

Yeung JT, Pollack IF, Shah S, Jaffe R, Nikiforova M, Jakacki RI.

Pediatr Blood Cancer. 2013 Jan;60(1):137-9. doi: 10.1002/pbc.24254. Epub 2012 Jul 27.

PubMed [citation]

PMID:: 22848017

See all PubMed Citations (5)

Details of each submission

From Women's Health and Genetics/Laboratory Corporation of America, LabCorp, SCV001442589.1

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

Description

Variant summary: PMS2 c.823C>T (p.Gln275X) 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 allele was found at a frequency of 8e-06 in 251410 control chromosomes (gnomAD). c.823C>T has been reported in the literature in multiple individuals affected with colorectal cancer and Lynch syndrome (Yeung_2013, Hansen_2014, ten Broeke_2015, van der Klift_2016, Wang_2020). These data indicate that the variant is very likely to be associated with disease. To our knowledge, no experimental evidence demonstrating an impact on protein function has been reported. Six ClinVar submitters (evaluation after 2014) cite 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: Apr 20, 2024

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